rs1213018336

Variant names:

• chr17-44354533-C-G
• rs1213018336
• NM_198475.3:c.1681G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-44354533-C-G
• chr17-44354533-C-T

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.1681G>C​(p.Glu561Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000975 in 1,025,426 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. E561K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.8e-7 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• 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=0.14827597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3	c.1681G>C	p.Glu561Gln	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2
FAM171A2	XM_017024490.2	c.1129G>C	p.Glu377Gln	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.1681G>C	p.Glu561Gln	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.75e-7 AC: 1 AN: 1025426 Hom.: 0 Cov.: 31 AF XY: 0.00000207 AC XY: 1 AN XY: 483786

African (AFR) AF: 0.0000482 AC: 1 AN: 20738

American (AMR) AF: 0.00 AC: 0 AN: 6708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11546

East Asian (EAS) AF: 0.00 AC: 0 AN: 21786

South Asian (SAS) AF: 0.00 AC: 0 AN: 19070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2588

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 883928

Other (OTH) AF: 0.00 AC: 0 AN: 39606

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	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.041
Sift	Benign	0.25	T
Sift4G	Benign	0.40	T
Polyphen		0.44	B
Vest4		0.077
MutPred		0.34		Gain of glycosylation at P564 (P = 0.1864);
MVP		0.040
ClinPred		0.39	T
GERP RS		3.1
Varity_R		0.17
gMVP		0.35
Mutation Taster		=95/5	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: rs1213018336; hg19: chr17-42431901;