1-50441487-C-T

Variant names:

• chr1-50441487-C-T
• NM_007051.3:c.1906G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007051.3(FAF1):​c.1906G>A​(p.Val636Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,393,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAF1 NM_007051.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

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]

FAF1-AS1 (HGNC:40228): (FAF1 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21944949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAF1	NM_007051.3	c.1906G>A	p.Val636Ile	missense_variant	Exon 19 of 19	ENST00000396153.7	NP_008982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAF1	ENST00000396153.7	c.1906G>A	p.Val636Ile	missense_variant	Exon 19 of 19	1	NM_007051.3	ENSP00000379457.2
FAF1	ENST00000494400.5	n.*330G>A		non_coding_transcript_exon_variant	Exon 14 of 14	2		ENSP00000434929.1
FAF1	ENST00000494400.5	n.*330G>A		3_prime_UTR_variant	Exon 14 of 14	2		ENSP00000434929.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1393764 Hom.: 0 Cov.: 28 AF XY: 0.00000146 AC XY: 1 AN XY: 686512

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.31e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1906G>A (p.V636I) alteration is located in exon 19 (coding exon 19) of the FAF1 gene. This alteration results from a G to A substitution at nucleotide position 1906, causing the valine (V) at amino acid position 636 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	Benign	0.11
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.0012
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.18	N;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.38	N;.
REVEL	Benign	0.10
Sift	Uncertain	0.029	D;.
Sift4G	Benign	0.14	T;T
Polyphen		0.011	B;.
Vest4		0.26
MutPred		0.49		Loss of methylation at K637 (P = 0.0545);.;
MVP		0.40
MPC		1.0
ClinPred		0.55	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-50907159;