Genetic Variant FAM171B:p.Ala201Ser (chr2-186747127-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177454.4(FAM171B):c.601G>T(p.Ala201Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,449,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FAM171B
NM_177454.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

FAM171B (HGNC:29412): (family with sequence similarity 171 member B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM171B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.079034775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171B	NM_177454.4 link	c.601G>T	p.Ala201Ser	missense_variant	Exon 4 of 8	ENST00000304698.10	NP_803237.3	Q6P995-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM171B	ENST00000304698.10 link	c.601G>T	p.Ala201Ser	missense_variant	Exon 4 of 8	1	NM_177454.4	ENSP00000304108.5		Q6P995-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

241950

Hom.:

AF XY:

0.00000764

AC XY:

AN XY:

130830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1449866

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

720970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.601G>T (p.A201S) alteration is located in exon 4 (coding exon 4) of the FAM171B gene. This alteration results from a G to T substitution at nucleotide position 601, causing the alanine (A) at amino acid position 201 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

0.074

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

PrimateAI

Benign

0.34

PROVEAN

Benign

0.36

N;.

REVEL

Benign

0.037

Sift

Benign

0.60

T;.

Sift4G

Benign

0.98

T;T

Polyphen

0.0030

B;.

Vest4

0.14

MVP

0.20

MPC

0.25

ClinPred

0.19

GERP RS

4.4

Varity_R

0.040

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over