10-124623580-T-C

Variant names:

• chr10-124623580-T-C
• NM_014661.4:c.931A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014661.4(FAM53B):​c.931A>G​(p.Ser311Gly) 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. 13/20 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: 2.67

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

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=0.21030477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53B	NM_014661.4	c.931A>G	p.Ser311Gly	missense_variant	Exon 5 of 5	ENST00000337318.8	NP_055476.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM53B	ENST00000337318.8	c.931A>G	p.Ser311Gly	missense_variant	Exon 5 of 5	1	NM_014661.4	ENSP00000338532.3
ENSG00000258539	ENST00000494792.1	n.*1104-4787A>G		intron_variant	Intron 9 of 9	5		ENSP00000455755.1
FAM53B	ENST00000392754.7	c.931A>G	p.Ser311Gly	missense_variant	Exon 5 of 5	2		ENSP00000376509.3
ENSG00000278831	ENST00000621254.1	n.228T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.931A>G (p.S311G) alteration is located in exon 5 (coding exon 4) of the FAM53B gene. This alteration results from a A to G substitution at nucleotide position 931, causing the serine (S) at amino acid position 311 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.060
Sift	Benign	0.12	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.59	P;P
Vest4		0.35
MutPred		0.40		Loss of stability (P = 0.0595);Loss of stability (P = 0.0595);
MVP		0.23
MPC		0.75
ClinPred		0.86	D
GERP RS		4.0
Varity_R		0.12
gMVP		0.23

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: chr10-126312149;