17-44354047-G-T

Variant names:

• chr17-44354047-G-T
• rs1254842624
• NM_198475.3:c.2167C>A

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.2167C>A​(p.Arg723Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000997 in 1,002,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R723C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• 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=0.16440085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3	c.2167C>A	p.Arg723Ser	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2
FAM171A2	XM_017024490.2	c.1615C>A	p.Arg539Ser	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.2167C>A	p.Arg723Ser	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.97e-7 AC: 1 AN: 1002726 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 472150

⚠️ 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: 19980

American (AMR) AF: 0.00 AC: 0 AN: 5894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10768

East Asian (EAS) AF: 0.00 AC: 0 AN: 19376

South Asian (SAS) AF: 0.00 AC: 0 AN: 18878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2492

European-Non Finnish (NFE) AF: 0.00000115 AC: 1 AN: 869952

Other (OTH) AF: 0.00 AC: 0 AN: 37940

⚠️ 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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N
PhyloP100		0.60
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.035
Sift	Uncertain	0.017	D
Sift4G	Benign	0.083	T
Polyphen		0.69	P
Vest4		0.20
MutPred		0.49		Gain of phosphorylation at R723 (P = 0.0035);
MVP		0.081
ClinPred		0.52	D
GERP RS		3.0
Varity_R		0.23
gMVP		0.28

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: rs1254842624; hg19: chr17-42431415;