Genetic Variant FAM171A2:p.Glu745Gly (chr17-44353980-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198475.3(FAM171A2):c.2234A>G(p.Glu745Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 149,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 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: 4.37

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3 link	c.2234A>G	p.Glu745Gly	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2	A8MVW0
FAM171A2	XM_017024490.2 link	c.1682A>G	p.Glu561Gly	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.2234A>G	p.Glu745Gly	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6		A8MVW0

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

149884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00110

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1134426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

549732

African (AFR)

AF:

0.00

AC:

AN:

22288

American (AMR)

AF:

0.00

AC:

AN:

9264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14478

East Asian (EAS)

AF:

0.00

AC:

AN:

24540

South Asian (SAS)

AF:

0.00

AC:

AN:

38910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2984

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

951762

Other (OTH)

AF:

0.00

AC:

AN:

44862

GnomAD4 genome

AF:

0.0000267

AC:

AN:

149884

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73166

show subpopulations

African (AFR)

AF:

0.0000730

AC:

AN:

41084

American (AMR)

AF:

0.00

AC:

AN:

15096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5068

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9760

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67330

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2234A>G (p.E745G) alteration is located in exon 8 (coding exon 8) of the FAM171A2 gene. This alteration results from a A to G substitution at nucleotide position 2234, causing the glutamic acid (E) at amino acid position 745 to be replaced by a glycine (G). 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

Pathogenic

0.82

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.7

PhyloP100

4.4

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.37

Sift

Uncertain

0.0030

Sift4G

Benign

0.065

Polyphen

1.0

Vest4

0.48

MutPred

0.61

Loss of solvent accessibility (P = 0.0769);

MVP

0.21

ClinPred

0.99

GERP RS

3.5

Varity_R

0.60

gMVP

0.39

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

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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