rs10736889

chr10-124650088-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014661.4(FAM53B):c.907-26484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,054 control chromosomes in the GnomAD database, including 23,193 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23193 hom., cov: 32)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM53B	NM_014661.4	c.907-26484T>C		intron_variant		ENST00000337318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM53B	ENST00000337318.8	c.907-26484T>C		intron_variant		1	NM_014661.4	P1
FAM53B	ENST00000392754.7	c.907-26484T>C		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82638 AN: 151936 Hom.: 23177 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.567

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.544 AC: 82684 AN: 152054 Hom.: 23193 Cov.: 32 AF XY: 0.539 AC XY: 40104 AN XY: 74346

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.544

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.563

Alfa AF: 0.585 Hom.: 4450

Bravo AF: 0.542

Asia WGS AF: 0.463 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	11
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10736889; hg19: chr10-126338657;