Variant chr22-50548690-A-C 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_138433.5(KLHDC7B):c.2447A>C(p.Lys816Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,520,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

KLHDC7B
NM_138433.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.498

Variant links:

Genes affected

KLHDC7B (HGNC:25145): (kelch domain containing 7B)

KLHDC7B links:

Genome browser will be placed here

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=0.106710404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7B	NM_138433.5 linkuse as main transcript	c.2447A>C	p.Lys816Thr	missense_variant	1/1	ENST00000648057.3	NP_612442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC7B	ENST00000648057.3 linkuse as main transcript	c.2447A>C	p.Lys816Thr	missense_variant	1/1		NM_138433.5	ENSP00000497256	P3
KLHDC7B	ENST00000395676.4 linkuse as main transcript	c.524A>C	p.Lys175Thr	missense_variant	1/1			ENSP00000379034	A2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.31e-7

AC:

AN:

1368536

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

673076

show subpopulations

Gnomad4 AFR exome

AF:

0.0000341

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Nov 01, 2022

The c.524A>C (p.K175T) alteration is located in exon 1 (coding exon 1) of the KLHDC7B gene. This alteration results from a A to C substitution at nucleotide position 524, causing the lysine (K) at amino acid position 175 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0055

.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.50

T;T

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.2

.;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.8

.;N

REVEL

Benign

0.28

Sift

Benign

0.054

.;T

Sift4G

Benign

0.27

.;T

Polyphen

0.60

.;P

Vest4

0.32

MutPred

0.25

.;Loss of ubiquitination at K175 (P = 0.0017);

MVP

0.62

ClinPred

0.14

GERP RS

-1.6

Varity_R

0.085

gMVP

0.49

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