Variant 12-49889186-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012306.4(FAIM2):c.668G>A(p.Cys223Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 1,611,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

FAIM2
NM_012306.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

FAIM2 (HGNC:17067): (Fas apoptotic inhibitory molecule 2) Involved in regulation of neuron apoptotic process. Acts upstream of or within negative regulation of extrinsic apoptotic signaling pathway via death domain receptors. Located in membrane raft. [provided by Alliance of Genome Resources, Apr 2022]

FAIM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038730115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAIM2	NM_012306.4 link	c.668G>A	p.Cys223Tyr	missense_variant	10/12	ENST00000320634.8	NP_036438.2	Q9BWQ8-1
FAIM2	XM_005268730.4 link	c.542G>A	p.Cys181Tyr	missense_variant	9/11		XP_005268787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAIM2	ENST00000320634.8 link	c.668G>A	p.Cys223Tyr	missense_variant	10/12	1	NM_012306.4	ENSP00000321951.3		Q9BWQ8-1

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000102

AC:

AN:

244832

Hom.:

AF XY:

0.0000605

AC XY:

AN XY:

132150

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000398

AC:

AN:

1459010

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

725408

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.0000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.000427

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000504

Hom.:

Bravo

AF:

0.000453

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

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

Aug 22, 2023

The c.668G>A (p.C223Y) alteration is located in exon 10 (coding exon 10) of the FAIM2 gene. This alteration results from a G to A substitution at nucleotide position 668, causing the cysteine (C) at amino acid position 223 to be replaced by a tyrosine (Y). 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

0.21

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

T;.;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.067

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.89

L;.;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-7.9

D;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.064

T;T;T;T

Sift4G

Benign

0.22

T;T;T;.

Polyphen

0.0020

B;.;.;.

Vest4

0.32

MVP

0.29

MPC

0.65

ClinPred

0.089

GERP RS

4.6

Varity_R

0.64

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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