chr1-231224289-A-G

Variant names:

• chr1-231224289-A-G
• rs199681084
• NM_152379.4:c.872T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152379.4(FSAF1):​c.872T>C​(p.Val291Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,606,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: FSAF1 NM_152379.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• Publications: 1 publications found

Genes affected

FSAF1 (HGNC:25332): (chromosome 1 open reading frame 131) Enables RNA binding activity. Located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11676642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FSAF1	NM_152379.4	c.872T>C	p.Val291Ala	missense_variant	Exon 7 of 7	ENST00000366649.7	NP_689592.2
FSAF1	NM_001300830.2	c.869T>C	p.Val290Ala	missense_variant	Exon 7 of 7		NP_001287759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1orf131	ENST00000366649.7	c.872T>C	p.Val291Ala	missense_variant	Exon 7 of 7	1	NM_152379.4	ENSP00000355609.2

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000110 AC: 27 AN: 244376 AF XY: 0.000106

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.0000615

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.000336

GnomAD4 exome AF: 0.000125 AC: 182 AN: 1454492 Hom.: 0 Cov.: 30 AF XY: 0.000131 AC XY: 95 AN XY: 723552

African (AFR) AF: 0.00 AC: 0 AN: 32812

American (AMR) AF: 0.000259 AC: 11 AN: 42414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25804

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.0000355 AC: 3 AN: 84596

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53312

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5716

European-Non Finnish (NFE) AF: 0.000134 AC: 149 AN: 1110152

Other (OTH) AF: 0.000267 AC: 16 AN: 60032

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.000229 AC XY: 17 AN XY: 74322

African (AFR) AF: 0.0000483 AC: 2 AN: 41426

American (AMR) AF: 0.00131 AC: 20 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68028

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000230 Hom.: 0

Bravo AF: 0.000393

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 30, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.872T>C (p.V291A) alteration is located in exon 7 (coding exon 7) of the C1orf131 gene. This alteration results from a T to C substitution at nucleotide position 872, causing the valine (V) at amino acid position 291 to be replaced by an alanine (A). 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	0.29
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	.;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.61	T
PhyloP100		1.9
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.13	T;T;T
Vest4		0.15
MVP		0.61
MPC		0.31
ClinPred		0.079	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.29
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs199681084; hg19: chr1-231360035;