17-44354047-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198475.3(FAM171A2):​c.2167C>T​(p.Arg723Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.605

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2940204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3	c.2167C>T	p.Arg723Cys	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2
FAM171A2	XM_017024490.2	c.1615C>T	p.Arg539Cys	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>T	p.Arg723Cys	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1002726 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 472150

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 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

Dec 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2167C>T (p.R723C) alteration is located in exon 8 (coding exon 8) of the FAM171A2 gene. This alteration results from a C to T substitution at nucleotide position 2167, causing the arginine (R) at amino acid position 723 to be replaced by a cysteine (C). 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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.069
Eigen_PC	Benign	-0.019
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PrimateAI	Pathogenic	0.94	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.54		Gain of catalytic residue at P722 (P = 0.0233);
MVP		0.17
ClinPred		0.89	D
GERP RS		3.0
Varity_R		0.31
gMVP		0.27

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: rs1254842624; hg19: chr17-42431415;