rs1294823709

Variant names:

• chr17-44354515-C-A
• rs1294823709
• NM_198475.3:c.1699G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-44354515-C-A
• chr17-44354515-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198475.3(FAM171A2):​c.1699G>T​(p.Gly567Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 986,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G567S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

FAM171A2 (HGNC:30480): (family with sequence similarity 171 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26042545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3	c.1699G>T	p.Gly567Cys	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2
FAM171A2	XM_017024490.2	c.1147G>T	p.Gly383Cys	missense_variant	Exon 6 of 6		XP_016879979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM171A2	ENST00000293443.12	c.1699G>T	p.Gly567Cys	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 986026 Hom.: 0 Cov.: 31 AF XY: 0.00000215 AC XY: 1 AN XY: 464364

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19636

American (AMR) AF: 0.00 AC: 0 AN: 5512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9972

East Asian (EAS) AF: 0.00 AC: 0 AN: 17362

South Asian (SAS) AF: 0.0000537 AC: 1 AN: 18636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2412

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 858458

Other (OTH) AF: 0.00 AC: 0 AN: 36940

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0060	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.36	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.12
Sift	Benign	0.057	T
Sift4G	Uncertain	0.045	D
Polyphen		1.0	D
Vest4		0.18
MutPred		0.46		Loss of relative solvent accessibility (P = 0.0186);
MVP		0.17
ClinPred		0.45	T
GERP RS		3.1
Varity_R		0.14
gMVP		0.43

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: rs1294823709; hg19: chr17-42431883;