6-73242057-C-T

Position:

chr6-73242057-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000257765.10(KHDC1):c.293G>A(p.Arg98Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,610,140 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

KHDC1
ENST00000257765.10 missense, splice_region

Scores

Splicing: ADA: 0.00003349

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.766

Variant links:

Genes affected

KHDC1 (HGNC:21366): (KH domain containing 1) Predicted to enable identical protein binding activity and poly(U) RNA binding activity. Predicted to be involved in activation of cysteine-type endopeptidase activity involved in apoptotic process. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

KHDC1 links:

LOC122539213 (HGNC:):

LOC122539213 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050726563).

BP6

Variant 6-73242057-C-T is Benign according to our data. Variant chr6-73242057-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2364682.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-73242057-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDC1	NM_030568.5 linkuse as main transcript	c.293G>A	p.Arg98Gln	missense_variant, splice_region_variant	3/4	ENST00000257765.10	NP_085045.3
LOC122539213	NR_173146.1 linkuse as main transcript	n.957G>A		splice_region_variant, non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHDC1	ENST00000257765.10 linkuse as main transcript	c.293G>A	p.Arg98Gln	missense_variant, splice_region_variant	3/4	1	NM_030568.5	ENSP00000257765	P2	Q4VXA5-2
KHDC1	ENST00000370384.7 linkuse as main transcript	c.512G>A	p.Arg171Gln	missense_variant, splice_region_variant	4/5	1		ENSP00000359411	A2	Q4VXA5-1
KHDC1	ENST00000433730.1 linkuse as main transcript	c.293G>A	p.Arg98Gln	missense_variant	3/3	3		ENSP00000406966

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000200

AC:

AN:

244816

Hom.:

AF XY:

0.000173

AC XY:

AN XY:

132784

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000235

Gnomad OTH exome

AF:

0.000841

GnomAD4 exome

AF:

0.000152

AC:

222

AN:

1457934

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

725070

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000541

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000348

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.000408

ESP6500AA

AF:

0.000249

AC:

ESP6500EA

AF:

0.000359

AC:

ExAC

AF:

0.000141

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.57

DANN

Benign

0.70

DEOGEN2

Benign

0.0069

.;T;.;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.68

.;T;T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.029

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.20

.;N;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.9

N;N;.;.;N

REVEL

Benign

0.048

Sift

Benign

0.31

T;.;.;.;T

Sift4G

Benign

0.12

T;T;T;T;.

Polyphen

0.18

.;B;.;.;.

Vest4

0.13

MVP

0.014

MPC

0.048

ClinPred

0.0058

GERP RS

-2.9

Varity_R

0.27

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0020

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

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