dbSNP rs375361851: FAM53B:p.Ala315Ser (chr10-124623568-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014661.4(FAM53B):c.943G>T(p.Ala315Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FAM53B
NM_014661.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Variant links:

Genes affected

FAM53B (HGNC:28968): (family with sequence similarity 53 member B) Involved in positive regulation of canonical Wnt signaling pathway. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM53B links:

ENSG00000258539 (HGNC:):

ENSG00000258539 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024850458).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53B	NM_014661.4 link	c.943G>T	p.Ala315Ser	missense_variant	Exon 5 of 5	ENST00000337318.8	NP_055476.3	Q14153-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM53B	ENST00000337318.8 link	c.943G>T	p.Ala315Ser	missense_variant	Exon 5 of 5	1	NM_014661.4	ENSP00000338532.3	Q14153-1
ENSG00000258539	ENST00000494792.1 link	n.*1104-4775G>T		intron_variant	Intron 9 of 9	5		ENSP00000455755.1	H3BQF6
FAM53B	ENST00000392754.7 link	c.943G>T	p.Ala315Ser	missense_variant	Exon 5 of 5	2		ENSP00000376509.3	Q14153-1
ENSG00000278831	ENST00000621254.1 link	n.216C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454074

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722918

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.39

DANN

Benign

0.77

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.47

.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

0.57

N;N

REVEL

Benign

0.019

Sift

Benign

0.40

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0050

B;B

Vest4

0.033

MutPred

0.20

Gain of glycosylation at A315 (P = 0.0131);Gain of glycosylation at A315 (P = 0.0131);

MVP

0.13

MPC

0.34

ClinPred

0.030

GERP RS

-6.1

Varity_R

0.015

gMVP

0.083

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over