dbSNP rs654128: FAM162B:p.Gln71His (chr6-116765215-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001085480.3(FAM162B):c.213G>T(p.Gln71His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,613,708 control chromosomes in the GnomAD database, including 16,764 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1368 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15396 hom. )

Consequence

FAM162B
NM_001085480.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Variant links:

Genes affected

FAM162B (HGNC:21549): (family with sequence similarity 162 member B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM162B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001049012).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM162B	NM_001085480.3 link	c.213G>T	p.Gln71His	missense_variant	Exon 2 of 4	ENST00000368557.6	NP_001078949.1	Q5T6X4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM162B	ENST00000368557.6 link	c.213G>T	p.Gln71His	missense_variant	Exon 2 of 4	1	NM_001085480.3	ENSP00000357545.4		Q5T6X4

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19115

AN:

152026

Hom.:

1371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0931

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.0571

Gnomad SAS

AF:

0.0371

Gnomad FIN

AF:

0.0982

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.119

AC:

29757

AN:

249242

Hom.:

2249

AF XY:

0.120

AC XY:

16162

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.0916

Gnomad AMR exome

AF:

0.0906

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.0481

Gnomad SAS exome

AF:

0.0426

Gnomad FIN exome

AF:

0.0932

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.140

AC:

204018

AN:

1461564

Hom.:

15396

Cov.:

AF XY:

0.138

AC XY:

100415

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0957

Gnomad4 AMR exome

AF:

0.0955

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.0536

Gnomad4 SAS exome

AF:

0.0427

Gnomad4 FIN exome

AF:

0.0933

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.126

AC:

19106

AN:

152144

Hom.:

1368

Cov.:

AF XY:

0.122

AC XY:

9042

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0928

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.282

Gnomad4 EAS

AF:

0.0572

Gnomad4 SAS

AF:

0.0367

Gnomad4 FIN

AF:

0.0982

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.156

Alfa

AF:

0.155

Hom.:

4267

Bravo

AF:

0.129

TwinsUK

AF:

0.136

AC:

505

ALSPAC

AF:

0.147

AC:

565

ESP6500AA

AF:

0.0939

AC:

407

ESP6500EA

AF:

0.158

AC:

1354

ExAC

AF:

0.117

AC:

14172

Asia WGS

AF:

0.0610

AC:

215

AN:

3478

EpiCase

AF:

0.172

EpiControl

AF:

0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0075

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

REVEL

Benign

0.12

Sift

Benign

0.081

Sift4G

Benign

0.18

Polyphen

0.97

Vest4

0.086

MutPred

0.12

Loss of MoRF binding (P = 0.1028);

MPC

1.2

ClinPred

0.068

GERP RS

-7.3

Varity_R

0.43

gMVP

0.41

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over