Genetic Variant FAM171A2:p.Gly567Ser (chr17-44354515-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.1699G>A(p.Gly567Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 147,932 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: 0.0000041 ( 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: 1.19

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=0.16424501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3 link	c.1699G>A	p.Gly567Ser	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2	A8MVW0
FAM171A2	XM_017024490.2 link	c.1147G>A	p.Gly383Ser	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.1699G>A	p.Gly567Ser	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6		A8MVW0

Frequencies

GnomAD3 genomes

AF:

0.0000203

AC:

AN:

147834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000201

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: AS_VQSR

AF:

0.00000406

AC:

AN:

986026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

464364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19636

American (AMR)

AF:

0.000544

AC:

AN:

5512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9972

East Asian (EAS)

AF:

0.00

AC:

AN:

17362

South Asian (SAS)

AF:

0.00

AC:

AN:

18636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2412

European-Non Finnish (NFE)

AF:

0.00000116

AC:

AN:

858458

Other (OTH)

AF:

0.00

AC:

AN:

36940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000203

AC:

AN:

147932

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41056

American (AMR)

AF:

0.000201

AC:

AN:

14948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3398

East Asian (EAS)

AF:

0.00

AC:

AN:

5078

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66402

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 05, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1699G>A (p.G567S) 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 1699, causing the glycine (G) at amino acid position 567 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

0.099

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.46

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

1.2

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.74

REVEL

Benign

0.061

Sift

Benign

0.74

Sift4G

Benign

0.74

Polyphen

0.96

Vest4

0.058

MutPred

0.33

Gain of glycosylation at G567 (P = 4e-04);

MVP

0.040

ClinPred

0.35

GERP RS

3.1

Varity_R

0.042

gMVP

0.38

Mutation Taster

=89/11

polymorphism

(source)

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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17-44354515-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over