Genetic Variant FAM167B:p.Gly4Glu (chr1-32247432-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_032648.3(FAM167B):c.11G>A(p.Gly4Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000966 in 1,555,102 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 2 hom. )

Consequence

FAM167B
NM_032648.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

FAM167B (HGNC:28133): (family with sequence similarity 167 member B)

FAM167B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00226897).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM167B	NM_032648.3 link	c.11G>A	p.Gly4Glu	missense_variant	Exon 1 of 2	ENST00000373582.4	NP_116037.2	Q9BTA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM167B	ENST00000373582.4 link	c.11G>A	p.Gly4Glu	missense_variant	Exon 1 of 2	1	NM_032648.3	ENSP00000362684.3		Q9BTA0

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000889

AC:

182

AN:

204762

Hom.:

AF XY:

0.000820

AC XY:

AN XY:

109766

show subpopulations

Gnomad AFR exome

AF:

0.0000699

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000240

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.00124

Gnomad OTH exome

AF:

0.000622

GnomAD4 exome

AF:

0.000945

AC:

1325

AN:

1402818

Hom.:

Cov.:

AF XY:

0.000901

AC XY:

624

AN XY:

692374

show subpopulations

Gnomad4 AFR exome

AF:

0.000283

Gnomad4 AMR exome

AF:

0.00113

Gnomad4 ASJ exome

AF:

0.0000436

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.000262

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

152284

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00137

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00126

Hom.:

Bravo

AF:

0.00128

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000244

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000918

AC:

111

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.11G>A (p.G4E) alteration is located in exon 1 (coding exon 1) of the FAM167B gene. This alteration results from a G to A substitution at nucleotide position 11, causing the glycine (G) at amino acid position 4 to be replaced by a glutamic acid (E). 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

0.082

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.025

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.52

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.88

REVEL

Benign

0.058

Sift

Benign

0.064

Sift4G

Benign

0.066

Polyphen

0.0

Vest4

0.059

MVP

0.072

MPC

0.55

ClinPred

0.0069

GERP RS

3.7

Varity_R

0.043

gMVP

0.27

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