Genetic Variant FAM171A2:p.Gly740Ser (chr17-44353996-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198475.3(FAM171A2):c.2218G>A(p.Gly740Ser) 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Publications

0 publications found

Variant links:

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]

FAM171A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.17803955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3 link	c.2218G>A	p.Gly740Ser	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2	A8MVW0
FAM171A2	XM_017024490.2 link	c.1666G>A	p.Gly556Ser	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 link	c.2218G>A	p.Gly740Ser	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6		A8MVW0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1074884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

512158

African (AFR)

AF:

0.00

AC:

AN:

21600

American (AMR)

AF:

0.00

AC:

AN:

7508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13128

East Asian (EAS)

AF:

0.00

AC:

AN:

23536

South Asian (SAS)

AF:

0.00

AC:

AN:

26870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2784

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

915340

Other (OTH)

AF:

0.00

AC:

AN:

42046

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 20, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2218G>A (p.G740S) alteration is located in exon 8 (coding exon 8) of the FAM171A2 gene. This alteration results from a G to A substitution at nucleotide position 2218, causing the glycine (G) at amino acid position 740 to be replaced by a serine (S). 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

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0015

Eigen

Benign

-0.054

Eigen_PC

Benign

-0.063

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

3.5

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

0.33

REVEL

Benign

0.098

Sift

Benign

0.58

Sift4G

Benign

0.38

Polyphen

0.63

Vest4

0.12

MutPred

0.29

Gain of phosphorylation at G740 (P = 0.0033);

MVP

0.048

ClinPred

0.71

GERP RS

3.0

Varity_R

0.13

gMVP

0.12

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over