7-130083867-T-G

Position:

• chr7-130083867-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KLHDC10	NM_014997.4	c.167-13054T>G		intron_variant		ENST00000335420.10	NP_055812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC10	ENST00000335420.10	c.167-13054T>G		intron_variant		1	NM_014997.4	ENSP00000334140	P1
KLHDC10	ENST00000463413.1	c.166+13058T>G		intron_variant		2		ENSP00000420083
KLHDC10	ENST00000468226.1	c.-300-11028T>G		intron_variant		3		ENSP00000420034

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

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.535

Alfa AF: 0.495 Hom.: 9260

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

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: rs10251765; hg19: chr7-129723707;