7-130083867-T-G

Variant names:

• chr7-130083867-T-G
• rs10251765
• NM_014997.4:c.167-13054T>G

Variant summary

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

The NM_014997.4(KLHDC10):​c.167-13054T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,938 control chromosomes in the GnomAD database, including 18,556 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 0.48 (18556 hom., cov: 31)
• Consequence: KLHDC10 NM_014997.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 7 publications found

Genes affected

KLHDC10 (HGNC:22194): (kelch domain containing 10) Enables ubiquitin ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in nucleoplasm. Is active in Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC10	NM_014997.4	c.167-13054T>G		intron_variant	Intron 1 of 9	ENST00000335420.10	NP_055812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC10	ENST00000335420.10	c.167-13054T>G		intron_variant	Intron 1 of 9	1	NM_014997.4	ENSP00000334140.4
KLHDC10	ENST00000468226.1	c.-300-11028T>G		intron_variant	Intron 1 of 6	3		ENSP00000420034.1
KLHDC10	ENST00000463413.1	c.166+13058T>G		intron_variant	Intron 1 of 2	2		ENSP00000420083.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72181 AN: 151818 Hom.: 18554 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.475 AC: 72204 AN: 151938 Hom.: 18556 Cov.: 31 AF XY: 0.478 AC XY: 35452 AN XY: 74234

African (AFR) AF: 0.267 AC: 11055 AN: 41450

American (AMR) AF: 0.584 AC: 8918 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2023 AN: 3472

East Asian (EAS) AF: 0.742 AC: 3828 AN: 5158

South Asian (SAS) AF: 0.495 AC: 2386 AN: 4822

European-Finnish (FIN) AF: 0.535 AC: 5629 AN: 10518

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36639 AN: 67936

Other (OTH) AF: 0.535 AC: 1129 AN: 2112

Alfa AF: 0.501 Hom.: 13314

Bravo AF: 0.471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		-2.1
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: rs10251765; hg19: chr7-129723707;