chr10-124623568-C-A

Variant names:

• chr10-124623568-C-A
• rs375361851
• NM_014661.4:c.943G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A315T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM53B NM_014661.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 0 publications found

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]

ENSG00000258539 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024850458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014661.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	NM_014661.4	MANE Select	c.943G>T	p.Ala315Ser	missense	Exon 5 of 5	NP_055476.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	ENST00000337318.8	TSL:1 MANE Select	c.943G>T	p.Ala315Ser	missense	Exon 5 of 5	ENSP00000338532.3	Q14153-1
	ENSG00000258539	ENST00000494792.1	TSL:5	n.*1104-4775G>T		intron	N/A	ENSP00000455755.1	H3BQF6
	FAM53B	ENST00000392754.7	TSL:2	c.943G>T	p.Ala315Ser	missense	Exon 5 of 5	ENSP00000376509.3	Q14153-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454074 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722918

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 43962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 85076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109926

Other (OTH) AF: 0.00 AC: 0 AN: 60132

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.39
DANN	Benign	0.77
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.5
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.57	N
REVEL	Benign	0.019
Sift	Benign	0.40	T
Sift4G	Benign	0.40	T
Polyphen		0.0050	B
Vest4		0.033
MutPred		0.20		Gain of glycosylation at A315 (P = 0.0131)
MVP		0.13
MPC		0.34
ClinPred		0.030	T
GERP RS		-6.1
Varity_R		0.015
gMVP		0.083
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs375361851; hg19: chr10-126312137;