rs1254842624

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-44354047-G-A
• chr17-44354047-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 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 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM171A2	NM_198475.3	MANE Select	c.2167C>T	p.Arg723Cys	missense	Exon 8 of 8	NP_940877.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM171A2	ENST00000293443.12	TSL:1 MANE Select	c.2167C>T	p.Arg723Cys	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
	FAM171A2	ENST00000912944.1		c.2203C>T	p.Arg735Cys	missense	Exon 9 of 9	ENSP00000583003.1
	FAM171A2	ENST00000912945.1		c.2194C>T	p.Arg732Cys	missense	Exon 8 of 8	ENSP00000583004.1

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

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: 0.00 AC: 0 AN: 869952

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.60
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

Other links and lift over

dbSNP: rs1254842624; hg19: chr17-42431415;