NM_198475.3:c.1751C>G

Variant names:

• chr17-44354463-G-C
• rs960547205
• NM_198475.3:c.1751C>G

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.1751C>G​(p.Pro584Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000107 in 936,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P584L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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=0.16059726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3	c.1751C>G	p.Pro584Arg	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2
FAM171A2	XM_017024490.2	c.1199C>G	p.Pro400Arg	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.1751C>G	p.Pro584Arg	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000107 AC: 1 AN: 936168 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 439568

African (AFR) AF: 0.00 AC: 0 AN: 18108

American (AMR) AF: 0.00 AC: 0 AN: 4022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8066

East Asian (EAS) AF: 0.00 AC: 0 AN: 11274

South Asian (SAS) AF: 0.00 AC: 0 AN: 18218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2156

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 825970

Other (OTH) AF: 0.00 AC: 0 AN: 33596

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.058
Sift	Benign	0.18	T
Sift4G	Benign	0.52	T
Polyphen		0.66	P
Vest4		0.086
MutPred		0.32		Gain of helix (P = 0.0325);
MVP		0.15
ClinPred		0.14	T
GERP RS		2.4
Varity_R		0.077
gMVP		0.21
Mutation Taster		=88/12	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: rs960547205; hg19: chr17-42431831;