chr10-124723355-G-A

Position:

• chr10-124723355-G-A

Variant summary

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

The NM_014661.4(FAM53B):​c.-174-16468C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,162 control chromosomes in the GnomAD database, including 8,783 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 0.33 (8783 hom., cov: 33)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM53B	NM_014661.4	c.-174-16468C>T		intron_variant		ENST00000337318.8	NP_055476.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM53B	ENST00000337318.8	c.-174-16468C>T		intron_variant		1	NM_014661.4	ENSP00000338532	P1
FAM53B	ENST00000280780.6	c.-174-16468C>T		intron_variant		1		ENSP00000280780
FAM53B	ENST00000392754.7	c.-174-16468C>T		intron_variant		2		ENSP00000376509	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50804 AN: 152044 Hom.: 8777 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.334 AC: 50828 AN: 152162 Hom.: 8783 Cov.: 33 AF XY: 0.329 AC XY: 24469 AN XY: 74414

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.357

Alfa AF: 0.361 Hom.: 20571

Bravo AF: 0.345

Asia WGS AF: 0.298 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.75

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: rs10794178; hg19: chr10-126411924;