Variant 6-43017622-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_057161.4(KLHDC3):c.258C>T(p.Asp86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,614,108 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 2 hom. )

Consequence

KLHDC3
NM_057161.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.59

Variant links:

Genes affected

KLHDC3 (HGNC:20704): (kelch domain containing 3) The protein encoded by this gene contains six repeated kelch motifs that are structurally similar to recombination activating gene 2, a protein involved in the activation of the V(D)J recombination. In mouse, this gene is found to be expressed specifically in testis. Its expression in pachytene spermatocytes is localized to cytoplasma and meiotic chromatin, suggesting that this gene may be involved in meiotic recombination. [provided by RefSeq, Jun 2012]

KLHDC3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 6-43017622-C-T is Benign according to our data. Variant chr6-43017622-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656571.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.59 with no splicing effect.

BS2

High AC in GnomAd4 at 81 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLHDC3	NM_057161.4 linkuse as main transcript	c.258C>T	p.Asp86=	synonymous_variant	3/11	ENST00000326974.9	NP_476502.1
KLHDC3	XM_047418163.1 linkuse as main transcript	c.258C>T	p.Asp86=	synonymous_variant	3/11		XP_047274119.1
KLHDC3	XM_047418164.1 linkuse as main transcript	c.258C>T	p.Asp86=	synonymous_variant	3/11		XP_047274120.1
KLHDC3	NR_040101.2 linkuse as main transcript	n.417C>T		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC3	ENST00000326974.9 linkuse as main transcript	c.258C>T	p.Asp86=	synonymous_variant	3/11	1	NM_057161.4	ENSP00000313995	P1
KLHDC3	ENST00000244670.12 linkuse as main transcript	c.-29C>T		5_prime_UTR_variant	3/10	1		ENSP00000244670

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000406

AC:

102

AN:

251282

Hom.:

AF XY:

0.000449

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000405

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000405

AC:

592

AN:

1461794

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

286

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00158

Gnomad4 AMR exome

AF:

0.000940

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000339

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000532

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000963

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000499

Hom.:

Bravo

AF:

0.000646

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

KLHDC3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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