ENST00000463909.1:n.2304G>A

Variant names:

• chr22-20997831-G-A
• rs3747081
• ENST00000463909.1:n.2304G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000463909.1(LZTR1):​n.2304G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0991 in 157,544 control chromosomes in the GnomAD database, including 1,011 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (986 hom., cov: 33)
  • Exomes 𝑓: 0.084 (25 hom.)
• Consequence: LZTR1 ENST00000463909.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 9 publications found

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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• Noonan syndrome 10

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• schwannomatosis

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• Noonan syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Noonan syndrome 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Genomics England PanelApp
• breast cancer

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ENSG00000285314 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LZTR1	NM_006767.4	c.*483G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000646124.2	NP_006758.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LZTR1	ENST00000646124.2	c.*483G>A		3_prime_UTR_variant	Exon 21 of 21		NM_006767.4	ENSP00000496779.1

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15155 AN: 151906 Hom.: 986 Cov.: 33

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0841

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0913

GnomAD4 exome AF: 0.0838 AC: 463 AN: 5522 Hom.: 25 Cov.: 0 AF XY: 0.0829 AC XY: 238 AN XY: 2870

African (AFR) AF: 0.0256 AC: 2 AN: 78

American (AMR) AF: 0.0799 AC: 93 AN: 1164

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 7 AN: 54

East Asian (EAS) AF: 0.119 AC: 21 AN: 176

South Asian (SAS) AF: 0.0918 AC: 45 AN: 490

European-Finnish (FIN) AF: 0.153 AC: 15 AN: 98

Middle Eastern (MID) AF: 0.0833 AC: 1 AN: 12

European-Non Finnish (NFE) AF: 0.0812 AC: 262 AN: 3228

Other (OTH) AF: 0.0766 AC: 17 AN: 222

GnomAD4 genome AF: 0.0997 AC: 15155 AN: 152022 Hom.: 986 Cov.: 33 AF XY: 0.105 AC XY: 7776 AN XY: 74324

African (AFR) AF: 0.0224 AC: 928 AN: 41390

American (AMR) AF: 0.0838 AC: 1282 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1113 AN: 5158

South Asian (SAS) AF: 0.136 AC: 657 AN: 4830

European-Finnish (FIN) AF: 0.201 AC: 2127 AN: 10590

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.122 AC: 8328 AN: 67990

Other (OTH) AF: 0.0947 AC: 199 AN: 2102

Alfa AF: 0.108 Hom.: 2327

Bravo AF: 0.0867

Asia WGS AF: 0.181 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.80
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3747081; hg19: chr22-21352120;