chr10-15213322-T-A

Position:

• chr10-15213322-T-A

Variant summary

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

The NM_001010924.2(FAM171A1):​c.2266A>T​(p.Arg756Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: FAM171A1 NM_001010924.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.861

Genes affected

FAM171A1 (HGNC:23522): (family with sequence similarity 171 member A1) Involved in regulation of cell shape and stress fiber assembly. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC105376433 (HGNC:):

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	UniProt
FAM171A1	NM_001010924.2	c.2266A>T	p.Arg756Trp	missense_variant	8/8	ENST00000378116.9
LOC105376433	XR_007062068.1	n.85+4651T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM171A1	ENST00000378116.9	c.2266A>T	p.Arg756Trp	missense_variant	8/8	1	NM_001010924.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000843 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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.2266A>T (p.R756W) alteration is located in exon 8 (coding exon 8) of the FAM171A1 gene. This alteration results from a A to T substitution at nucleotide position 2266, causing the arginine (R) at amino acid position 756 to be replaced by a tryptophan (W). 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	0.20
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.51
MutPred		0.48		Loss of methylation at R756 (P = 0.0162);
MVP		0.22
MPC		0.92
ClinPred		0.97	D
GERP RS		2.7
Varity_R		0.37
gMVP		0.29

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: rs1200882021; hg19: chr10-15255321;