NM_014997.4:c.253+1604T>C

Variant names:

• chr7-130098611-T-C
• rs17133163
• NM_014997.4:c.253+1604T>C

Variant summary

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

The NM_014997.4(KLHDC10):​c.253+1604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,038 control chromosomes in the GnomAD database, including 6,054 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 0.27 (6054 hom., cov: 32)
• Consequence: KLHDC10 NM_014997.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.862
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC10	NM_014997.4	c.253+1604T>C		intron_variant	Intron 2 of 9	ENST00000335420.10	NP_055812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC10	ENST00000335420.10	c.253+1604T>C		intron_variant	Intron 2 of 9	1	NM_014997.4	ENSP00000334140.4
KLHDC10	ENST00000468226.1	c.-177+1604T>C		intron_variant	Intron 3 of 6	3		ENSP00000420034.1
KLHDC10	ENST00000463413.1	c.167-17834T>C		intron_variant	Intron 1 of 2	2		ENSP00000420083.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40814 AN: 151920 Hom.: 6048 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.269 AC: 40851 AN: 152038 Hom.: 6054 Cov.: 32 AF XY: 0.266 AC XY: 19764 AN XY: 74320

African (AFR) AF: 0.352 AC: 14589 AN: 41472

American (AMR) AF: 0.168 AC: 2569 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3466

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5188

South Asian (SAS) AF: 0.171 AC: 827 AN: 4826

European-Finnish (FIN) AF: 0.324 AC: 3405 AN: 10508

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18070 AN: 67976

Other (OTH) AF: 0.213 AC: 449 AN: 2108

Alfa AF: 0.261 Hom.: 7157

Bravo AF: 0.262

Asia WGS AF: 0.107 AC: 375 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.3
DANN	Benign	0.72
PhyloP100		0.86
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: rs17133163; hg19: chr7-129738451;