Genetic Variant FAM171A2:p.Ser685Asn (chr17-44354160-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_198475.3(FAM171A2):c.2054G>A(p.Ser685Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000892 in 1,121,334 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 8.9e-7 ( 0 hom. )

Consequence

FAM171A2
NM_198475.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2714432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3 link	c.2054G>A	p.Ser685Asn	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2	A8MVW0
FAM171A2	XM_017024490.2 link	c.1502G>A	p.Ser501Asn	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.2054G>A	p.Ser685Asn	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6		A8MVW0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.92e-7

AC:

AN:

1121334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

542832

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21966

American (AMR)

AF:

0.00

AC:

AN:

8876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14856

East Asian (EAS)

AF:

0.00

AC:

AN:

25094

South Asian (SAS)

AF:

0.00

AC:

AN:

40952

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

934324

Other (OTH)

AF:

0.00

AC:

AN:

43686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Feb 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2054G>A (p.S685N) 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 2054, causing the serine (S) at amino acid position 685 to be replaced by an asparagine (N). 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

0.97

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.042

Eigen

Benign

0.030

Eigen_PC

Benign

-0.040

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

PhyloP100

3.7

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.5

REVEL

Benign

0.14

Sift

Benign

0.14

Sift4G

Benign

0.14

Polyphen

0.76

Vest4

0.079

MutPred

0.69

Loss of phosphorylation at S685 (P = 0.029);

MVP

0.048

ClinPred

0.72

GERP RS

3.0

Varity_R

0.34

gMVP

0.21

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