17-64860117-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_199340.5(LRRC37A3):c.4029G>A(p.Pro1343=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000433 in 1,613,936 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00045 (5 hom.)
• Consequence: LRRC37A3 NM_199340.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.08

Genes affected

LRRC37A3 (HGNC:32427): (leucine rich repeat containing 37 member A3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105376844 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-64860117-C-T is Benign according to our data. Variant chr17-64860117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.09 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37A3	NM_199340.5	c.4029G>A	p.Pro1343=	synonymous_variant	12/15	ENST00000584306.6
LOC105376844	XR_934912.4	n.177+10130C>T		intron_variant, non_coding_transcript_variant
LRRC37A3	NM_001303255.3	c.1383G>A	p.Pro461=	synonymous_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37A3	ENST00000584306.6	c.4029G>A	p.Pro1343=	synonymous_variant	12/15	1	NM_199340.5	P1

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152148 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000783 AC: 196 AN: 250350 Hom.: 1 AF XY: 0.00111 AC XY: 151 AN XY: 135604

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.00594

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000455 AC: 665 AN: 1461670 Hom.: 5 Cov.: 33 AF XY: 0.000637 AC XY: 463 AN XY: 727146

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.00652

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000270

Gnomad4 OTH exome AF: 0.000613

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152266 Hom.: 0 Cov.: 31 AF XY: 0.000336 AC XY: 25 AN XY: 74454

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000208 Hom.: 0

Bravo AF: 0.000132

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

LRRC37A3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.22
Dann	Benign	0.31

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: rs555242552; hg19: chr17-62856235; COSMIC: COSV58534376; COSMIC: COSV58534376;