Variant 19-35754050-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_019104.3(LIN37):c.478G>A(p.Val160Met) variant causes a missense change. The variant allele was found at a frequency of 0.000753 in 1,613,848 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 0 hom. )

Consequence

LIN37
NM_019104.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

Variant links:

Genes affected

LIN37 (HGNC:33234): (lin-37 DREAM MuvB core complex component) This gene encodes a protein expressed in the eye. [provided by RefSeq, Jul 2008]

LIN37 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33514822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LIN37	NM_019104.3 linkuse as main transcript	c.478G>A	p.Val160Met	missense_variant	7/9	ENST00000301159.14	NP_061977.1
LIN37	NM_001369780.1 linkuse as main transcript	c.436G>A	p.Val146Met	missense_variant	7/9		NP_001356709.1
LIN37	NR_163146.1 linkuse as main transcript	n.460G>A		non_coding_transcript_exon_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN37	ENST00000301159.14 linkuse as main transcript	c.478G>A	p.Val160Met	missense_variant	7/9	1	NM_019104.3	ENSP00000301159	P1

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.000794

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000333

AC:

AN:

249100

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

135192

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000620

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000790

AC:

1154

AN:

1461514

Hom.:

Cov.:

AF XY:

0.000681

AC XY:

495

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000407

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000580

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000720

AC:

ExAC

AF:

0.000256

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.478G>A (p.V160M) alteration is located in exon 7 (coding exon 7) of the LIN37 gene. This alteration results from a G to A substitution at nucleotide position 478, causing the valine (V) at amino acid position 160 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

M_CAP

Benign

0.010

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

REVEL

Benign

0.16

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.016

Polyphen

0.99

Vest4

0.57

MVP

0.59

MPC

0.57

ClinPred

0.12

GERP RS

5.2

Varity_R

0.20

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over