10-124658034-C-T

Variant names:

• chr10-124658034-C-T
• rs1006368
• NM_014661.4:c.906+23573G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014661.4(FAM53B):​c.906+23573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,186 control chromosomes in the GnomAD database, including 1,586 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 0.13 (1586 hom., cov: 33)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	NM_014661.4	MANE Select	c.906+23573G>A		intron	N/A	NP_055476.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	ENST00000337318.8	TSL:1 MANE Select	c.906+23573G>A		intron	N/A	ENSP00000338532.3
	ENSG00000258539	ENST00000494792.1	TSL:5	n.*1103+23573G>A		intron	N/A	ENSP00000455755.1
	FAM53B	ENST00000392754.7	TSL:2	c.906+23573G>A		intron	N/A	ENSP00000376509.3

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20487 AN: 152068 Hom.: 1584 Cov.: 33

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.135 AC: 20498 AN: 152186 Hom.: 1586 Cov.: 33 AF XY: 0.132 AC XY: 9825 AN XY: 74416

African (AFR) AF: 0.189 AC: 7854 AN: 41500

American (AMR) AF: 0.161 AC: 2465 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3470

East Asian (EAS) AF: 0.144 AC: 743 AN: 5176

South Asian (SAS) AF: 0.0882 AC: 426 AN: 4832

European-Finnish (FIN) AF: 0.0688 AC: 729 AN: 10596

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7492 AN: 68000

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.110 Hom.: 978

Bravo AF: 0.147

Asia WGS AF: 0.118 AC: 411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.72
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1006368; hg19: chr10-126346603;