1-50535437-A-T

Position:

• chr1-50535437-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007051.3(FAF1):​c.1426T>A​(p.Leu476Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 3.75

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAF1	NM_007051.3	c.1426T>A	p.Leu476Ile	missense_variant	15/19	ENST00000396153.7	NP_008982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAF1	ENST00000396153.7	c.1426T>A	p.Leu476Ile	missense_variant	15/19	1	NM_007051.3	ENSP00000379457.2
FAF1	ENST00000494400.5	n.844T>A		non_coding_transcript_exon_variant	9/14	2		ENSP00000434929.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.1426T>A (p.L476I) alteration is located in exon 15 (coding exon 15) of the FAF1 gene. This alteration results from a T to A substitution at nucleotide position 1426, causing the leucine (L) at amino acid position 476 to be replaced by an isoleucine (I). 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.069	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D;.
Sift4G	Benign	0.084	T;T
Polyphen		0.80	P;.
Vest4		0.75
MutPred		0.39		Gain of helix (P = 0.0034);.;
MVP		0.75
MPC		2.4
ClinPred		0.91	D
GERP RS		0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-51001109;