Variant 4-186157591-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001395294.1(FAM149A):c.1474A>G(p.Lys492Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00693 in 1,614,150 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 34)

Exomes 𝑓: 0.0071 ( 48 hom. )

Consequence

FAM149A
NM_001395294.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.49

Variant links:

Genes affected

FAM149A (HGNC:24527): (family with sequence similarity 149 member A)

FAM149A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061884224).

BP6

Variant 4-186157591-A-G is Benign according to our data. Variant chr4-186157591-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655216.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM149A	NM_001395294.1 linkuse as main transcript	c.1474A>G	p.Lys492Glu	missense_variant	8/14	ENST00000706927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM149A	ENST00000706927.1 linkuse as main transcript	c.1474A>G	p.Lys492Glu	missense_variant	8/14		NM_001395294.1	A2

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

743

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00789

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00514

AC:

1292

AN:

251428

Hom.:

AF XY:

0.00514

AC XY:

699

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.00808

Gnomad OTH exome

AF:

0.00652

GnomAD4 exome

AF:

0.00715

AC:

10446

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

4916

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.00846

Gnomad4 OTH exome

AF:

0.00498

GnomAD4 genome

AF:

0.00488

AC:

743

AN:

152378

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.00789

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00698

Hom.:

Bravo

AF:

0.00441

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00557

AC:

676

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00646

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

FAM149A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.012

.;T;.;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.75

.;T;.;.;T;T

MetaRNN

Benign

0.0062

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;M;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.14

T;T;T;T;T;T

Sift4G

Benign

0.073

T;D;T;T;T;T

Polyphen

0.22

.;B;.;.;.;.

Vest4

0.36

MVP

0.085

MPC

0.15

ClinPred

0.027

GERP RS

3.5

Varity_R

0.11

gMVP

0.18

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

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