chr10-124681807-A-C

Position:

• chr10-124681807-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014661.4(FAM53B):​c.706T>G​(p.Phe236Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: FAM53B NM_014661.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28651863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM53B	NM_014661.4	c.706T>G	p.Phe236Val	missense_variant	4/5	ENST00000337318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM53B	ENST00000337318.8	c.706T>G	p.Phe236Val	missense_variant	4/5	1	NM_014661.4	P1
FAM53B	ENST00000280780.6	c.706T>G	p.Phe236Val	missense_variant	4/5	1
FAM53B	ENST00000392754.7	c.706T>G	p.Phe236Val	missense_variant	4/5	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2021

The c.706T>G (p.F236V) alteration is located in exon 4 (coding exon 3) of the FAM53B gene. This alteration results from a T to G substitution at nucleotide position 706, causing the phenylalanine (F) at amino acid position 236 to be replaced by a valine (V). 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	0.29
BayesDel_addAF	Benign	-0.0026	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T;T;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	.;T;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M;M;M
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.041	D;D;D
Sift4G	Benign	0.066	T;T;T
Polyphen		0.89	P;P;B
Vest4		0.57
MutPred		0.29		Gain of phosphorylation at S237 (P = 0.1836);Gain of phosphorylation at S237 (P = 0.1836);Gain of phosphorylation at S237 (P = 0.1836);
MVP		0.51
MPC		0.62
ClinPred		0.48	T
GERP RS		5.1
Varity_R		0.083
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr10-126370376;