rs573275770

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6

The NM_006767.4(LZTR1):c.-4C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,549,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). The gene LZTR1 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LZTR1
NM_006767.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.642

Publications

0 publications found

Variant links:

Genes affected

LZTR1 (HGNC:6742): (leucine zipper like post translational regulator 1) This gene encodes a member of the BTB-kelch superfamily. Initially described as a putative transcriptional regulator based on weak homology to members of the basic leucine zipper-like family, the encoded protein subsequently has been shown to localize exclusively to the Golgi network where it may help stabilize the Gogli complex. Deletion of this gene may be associated with DiGeorge syndrome. [provided by RefSeq, Jul 2008]

LZTR1 Gene-Disease associations (from GenCC):

LZTR1-related schwannomatosis
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Noonan syndrome 10
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
schwannomatosis
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Noonan syndrome
Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Noonan syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp
breast cancer
Inheritance: AD Classification: MODERATE Submitted by: G2P
Costello syndrome
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
cardiofaciocutaneous syndrome
Inheritance: AR, AD Classification: NO_KNOWN Submitted by: ClinGen
Noonan syndrome-like disorder with loose anagen hair
Inheritance: AR, AD Classification: NO_KNOWN Submitted by: ClinGen

LZTR1 links:

ENSG00000285314 (HGNC:):

ENSG00000285314 links:

Genome browser will be placed here

ACMG classification

Specifications for LZTR1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 22-20982368-C-T is Benign according to our data. Variant chr22-20982368-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 561803.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006767.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LZTR1	NM_006767.4	MANE Select	c.-4C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	NP_006758.2
	LZTR1	NM_006767.4	MANE Select	c.-4C>T		5_prime_UTR	Exon 1 of 21	NP_006758.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LZTR1	ENST00000646124.2	MANE Select	c.-4C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000496779.1	Q8N653
LZTR1	ENST00000646124.2	MANE Select	c.-4C>T	5_prime_UTR	Exon 1 of 21	ENSP00000496779.1	Q8N653
LZTR1	ENST00000888029.1		c.-4C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000558088.1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000401

AC:

AN:

149454

AF XY:

0.0000373

show subpopulations

Gnomad AFR exome

AF:

0.000673

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.0000122

AC:

AN:

1396762

Hom.:

Cov.:

AF XY:

0.00000726

AC XY:

AN XY:

688620

show subpopulations

African (AFR)

AF:

0.000379

AC:

AN:

31652

American (AMR)

AF:

0.00

AC:

AN:

35758

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25052

East Asian (EAS)

AF:

0.00

AC:

AN:

35950

South Asian (SAS)

AF:

0.00

AC:

AN:

79492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077722

Other (OTH)

AF:

0.0000692

AC:

AN:

57830

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000718

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

-0.64

PromoterAI

-0.034

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over