Variant 7-130070736-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014997.4(KLHDC10):c.93T>G(p.Ser31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLHDC10
NM_014997.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0620

Variant links:

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]

KLHDC10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10073194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC10	NM_014997.4 linkuse as main transcript	c.93T>G	p.Ser31Arg	missense_variant	1/10	ENST00000335420.10	NP_055812.1	Q6PID8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLHDC10	ENST00000335420.10 linkuse as main transcript	c.93T>G	p.Ser31Arg	missense_variant	1/10	1	NM_014997.4	ENSP00000334140.4	Q6PID8-1
KLHDC10	ENST00000463413.1 linkuse as main transcript	c.93T>G	p.Ser31Arg	missense_variant	1/3	2		ENSP00000420083.1	C9JRT7
KLHDC10	ENST00000468226.1 linkuse as main transcript	c.-374T>G		upstream_gene_variant		3		ENSP00000420034.1	C9JRX2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000274

AC:

AN:

510094

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

250334

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000683

Gnomad4 FIN exome

AF:

0.000298

Gnomad4 NFE exome

AF:

0.0000176

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2024

The c.93T>G (p.S31R) alteration is located in exon 1 (coding exon 1) of the KLHDC10 gene. This alteration results from a T to G substitution at nucleotide position 93, causing the serine (S) at amino acid position 31 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.038

Sift

Benign

0.15

T;T

Sift4G

Benign

0.51

T;T

Polyphen

0.021

B;.

Vest4

0.26

MutPred

0.38

Gain of methylation at S31 (P = 6e-04);Gain of methylation at S31 (P = 6e-04);

MVP

0.15

MPC

1.2

ClinPred

0.27

GERP RS

-5.1

Varity_R

0.12

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over