chr10-15213274-G-T

Position:

• chr10-15213274-G-T

Variant summary

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

The NM_001010924.2(FAM171A1):​c.2314C>A​(p.His772Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM171A1 NM_001010924.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0775567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM171A1	NM_001010924.2	c.2314C>A	p.His772Asn	missense_variant	8/8	ENST00000378116.9
LOC105376433	XR_007062068.1	n.85+4603G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM171A1	ENST00000378116.9	c.2314C>A	p.His772Asn	missense_variant	8/8	1	NM_001010924.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461838 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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

Dec 20, 2023

The c.2314C>A (p.H772N) alteration is located in exon 8 (coding exon 8) of the FAM171A1 gene. This alteration results from a C to A substitution at nucleotide position 2314, causing the histidine (H) at amino acid position 772 to be replaced by an asparagine (N). 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	0.071
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.015
Sift	Benign	0.18	T
Sift4G	Benign	0.28	T
Polyphen		0.12	B
Vest4		0.11
MutPred		0.38		Loss of helix (P = 0.1299);
MVP		0.068
MPC		0.28
ClinPred		0.56	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.14

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: rs1833917435; hg19: chr10-15255273;