NM_014661.4:c.-174-6340T>C

Variant names:

• chr10-124713227-A-G
• rs4962399
• NM_014661.4:c.-174-6340T>C

Variant summary

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

The NM_014661.4(FAM53B):​c.-174-6340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,216 control chromosomes in the GnomAD database, including 1,121 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 0.11 (1121 hom., cov: 33)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 1 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]

FAM53B-AS1 (HGNC:49499): (FAM53B antisense RNA 1)

ENSG00000258539 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 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.-174-6340T>C		intron	N/A	NP_055476.3
	FAM53B-AS1	NR_120630.1		n.445-207A>G		intron	N/A
	FAM53B-AS1	NR_120631.1		n.305-207A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	ENST00000337318.8	TSL:1 MANE Select	c.-174-6340T>C		intron	N/A	ENSP00000338532.3
	FAM53B	ENST00000280780.6	TSL:1	c.-174-6340T>C		intron	N/A	ENSP00000280780.6
	FAM53B-AS1	ENST00000448422.3	TSL:1	n.708-207A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17314 AN: 152098 Hom.: 1120 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0632

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.114 AC: 17327 AN: 152216 Hom.: 1121 Cov.: 33 AF XY: 0.112 AC XY: 8303 AN XY: 74420

African (AFR) AF: 0.132 AC: 5469 AN: 41508

American (AMR) AF: 0.152 AC: 2333 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3468

East Asian (EAS) AF: 0.144 AC: 747 AN: 5174

South Asian (SAS) AF: 0.0624 AC: 301 AN: 4820

European-Finnish (FIN) AF: 0.0654 AC: 694 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7073 AN: 68010

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.118 Hom.: 180

Bravo AF: 0.124

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.78
PhyloP100		0.30
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: rs4962399; hg19: chr10-126401796;