Variant 1-18481360-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152375.3(KLHDC7A):c.379G>T(p.Gly127Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000782 in 1,607,114 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00041 ( 5 hom. )

Consequence

KLHDC7A
NM_152375.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.473

Variant links:

Genes affected

KLHDC7A (HGNC:26791): (kelch domain containing 7A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KLHDC7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005589813).

BP6

Variant 1-18481360-G-T is Benign according to our data. Variant chr1-18481360-G-T is described in ClinVar as [Benign]. Clinvar id is 716270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7A	NM_152375.3 linkuse as main transcript	c.379G>T	p.Gly127Cys	missense_variant	1/1	ENST00000400664.3	NP_689588.2	Q5VTJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC7A	ENST00000400664.3 linkuse as main transcript	c.379G>T	p.Gly127Cys	missense_variant	1/1	6	NM_152375.3	ENSP00000383505.1		Q5VTJ3

Frequencies

GnomAD3 genomes

AF:

0.00435

AC:

662

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00108

AC:

261

AN:

242090

Hom.:

AF XY:

0.000784

AC XY:

103

AN XY:

131436

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.000911

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.000515

GnomAD4 exome

AF:

0.000406

AC:

590

AN:

1454850

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

254

AN XY:

723244

show subpopulations

Gnomad4 AFR exome

AF:

0.0138

Gnomad4 AMR exome

AF:

0.000993

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000822

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.00438

AC:

667

AN:

152264

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00480

ESP6500AA

AF:

0.0124

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00118

AC:

143

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 02, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.78

REVEL

Benign

0.15

Sift

Benign

0.071

Sift4G

Benign

0.13

Polyphen

0.99

Vest4

0.22

MVP

0.52

MPC

1.1

ClinPred

0.013

GERP RS

2.3

Varity_R

0.087

gMVP

0.15

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