chr10-124681815-T-G

Variant names:

• chr10-124681815-T-G
• NM_014661.4:c.698A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014661.4(FAM53B):​c.698A>C​(p.His233Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.78
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

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.698A>C	p.His233Pro	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.698A>C	p.His233Pro	missense	Exon 4 of 5	ENSP00000338532.3	Q14153-1
	FAM53B	ENST00000280780.6	TSL:1	c.698A>C	p.His233Pro	missense	Exon 4 of 5	ENSP00000280780.6	Q14153-2
	ENSG00000258539	ENST00000494792.1	TSL:5	n.*895A>C		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	0.17
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.79
MutPred		0.37		Loss of sheet (P = 0.003)
MVP		0.73
MPC		1.4
ClinPred		0.83	D
GERP RS		4.8
Varity_R		0.43
gMVP		0.47
Mutation Taster		=56/44	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: chr10-126370384;