NM_014661.4:c.706T>G

Variant names:

• chr10-124681807-A-C
• NM_014661.4:c.706T>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 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
• 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: Uncertain_significance. The variant received 1 ACMG points.

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

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.706T>G	p.Phe236Val	missense	Exon 4 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.706T>G	p.Phe236Val	missense	Exon 4 of 5	ENSP00000338532.3	Q14153-1
	FAM53B	ENST00000280780.6	TSL:1	c.706T>G	p.Phe236Val	missense	Exon 4 of 5	ENSP00000280780.6	Q14153-2
	ENSG00000258539	ENST00000494792.1	TSL:5	n.*903T>G		non_coding_transcript_exon	Exon 9 of 10	ENSP00000455755.1	H3BQF6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.092
Sift	Benign	0.041	D
Sift4G	Benign	0.066	T
Polyphen		0.89	P
Vest4		0.57
MutPred		0.29		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
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

hg19: chr10-126370376;