NM_007051.3:c.946G>T

Variant names:

• chr1-50584706-C-A
• rs1651142090
• NM_007051.3:c.946G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007051.3(FAF1):​c.946G>T​(p.Ala316Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAF1 NM_007051.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

Genes affected

FAF1 (HGNC:3578): (Fas associated factor 1) Interaction of Fas ligand (TNFSF6) with the FAS antigen (TNFRSF6) mediates programmed cell death, also called apoptosis, in a number of organ systems. The protein encoded by this gene binds to FAS antigen and can initiate apoptosis or enhance apoptosis initiated through FAS antigen. Initiation of apoptosis by the protein encoded by this gene requires a ubiquitin-like domain but not the FAS-binding domain. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.06662732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAF1	NM_007051.3	c.946G>T	p.Ala316Ser	missense_variant	Exon 10 of 19	ENST00000396153.7	NP_008982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAF1	ENST00000396153.7	c.946G>T	p.Ala316Ser	missense_variant	Exon 10 of 19	1	NM_007051.3	ENSP00000379457.2
FAF1	ENST00000472808.1	n.300G>T		non_coding_transcript_exon_variant	Exon 3 of 7	3
FAF1	ENST00000494400.5	n.364G>T		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000434929.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.946G>T (p.A316S) alteration is located in exon 10 (coding exon 10) of the FAF1 gene. This alteration results from a G to T substitution at nucleotide position 946, causing the alanine (A) at amino acid position 316 to be replaced by a serine (S). 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	0.072
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.79
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.23
Sift	Benign	1.0	T
Sift4G	Benign	0.90	T
Polyphen		0.0050	B
Vest4		0.21
MutPred		0.20		Gain of phosphorylation at A316 (P = 0.012);
MVP		0.28
MPC		0.29
ClinPred		0.25	T
GERP RS		2.6
Varity_R		0.031
gMVP		0.15

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

Other links and lift over

dbSNP: rs1651142090; hg19: chr1-51050378;