rs1161258021

Variant names:

• chr17-44354395-C-T
• rs1161258021
• NM_198475.3:c.1819G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-44354395-C-T
• chr17-44354395-C-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.1819G>A​(p.Gly607Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,260,562 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.735
• 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=0.2040712).

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.1819G>A	p.Gly607Arg	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.1819G>A	p.Gly607Arg	missense	Exon 8 of 8	ENSP00000293443.6	A8MVW0
	FAM171A2	ENST00000912944.1		c.1855G>A	p.Gly619Arg	missense	Exon 9 of 9	ENSP00000583003.1
	FAM171A2	ENST00000912945.1		c.1846G>A	p.Gly616Arg	missense	Exon 8 of 8	ENSP00000583004.1

Frequencies

GnomAD3 genomes AF: 0.0000203 AC: 3 AN: 148010 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000450

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000255 AC: 1 AN: 39176 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000754

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000315 AC: 35 AN: 1112552 Hom.: 0 Cov.: 30 AF XY: 0.0000259 AC XY: 14 AN XY: 541532

African (AFR) AF: 0.00 AC: 0 AN: 21288

American (AMR) AF: 0.00 AC: 0 AN: 9670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14802

East Asian (EAS) AF: 0.00 AC: 0 AN: 22664

South Asian (SAS) AF: 0.00 AC: 0 AN: 38648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3980

European-Non Finnish (NFE) AF: 0.0000368 AC: 34 AN: 924144

Other (OTH) AF: 0.0000238 AC: 1 AN: 42072

GnomAD4 genome AF: 0.0000203 AC: 3 AN: 148010 Hom.: 0 Cov.: 32 AF XY: 0.0000277 AC XY: 2 AN XY: 72138

African (AFR) AF: 0.00 AC: 0 AN: 41012

American (AMR) AF: 0.00 AC: 0 AN: 14912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000450 AC: 3 AN: 66642

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

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	Benign	0.30
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.73
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.91	N
REVEL	Benign	0.076
Sift	Benign	0.15	T
Sift4G	Benign	0.28	T
Polyphen		0.95	P
Vest4		0.21
MutPred		0.45		Gain of MoRF binding (P = 0.0381)
MVP		0.076
ClinPred		0.063	T
GERP RS		2.0
Varity_R		0.10
gMVP		0.33
Mutation Taster		=89/11	polymorphism

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: rs1161258021; hg19: chr17-42431763;