rs3747081

Positions:

• chr22-20997831-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006767.4(LZTR1):​c.*483G>A variant causes a 3 prime UTR 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 NM_006767.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LZTR1	NM_006767.4	c.*483G>A		3_prime_UTR_variant	21/21	ENST00000646124.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LZTR1	ENST00000646124.2	c.*483G>A		3_prime_UTR_variant	21/21		NM_006767.4	P1

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

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.0799

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.0918

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.0812

Gnomad4 OTH exome AF: 0.0766

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

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.0838

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.115 Hom.: 1521

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

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

LitVar

Other links and lift over

dbSNP: rs3747081; hg19: chr22-21352120;