Variant 22-50548374-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138433.5(KLHDC7B):c.2131A>T(p.Thr711Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,551,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

KLHDC7B
NM_138433.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.818

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007489294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7B	NM_138433.5 linkuse as main transcript	c.2131A>T	p.Thr711Ser	missense_variant	1/1	ENST00000648057.3	NP_612442.3	Q96G42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC7B	ENST00000648057.3 linkuse as main transcript	c.2131A>T	p.Thr711Ser	missense_variant	1/1		NM_138433.5	ENSP00000497256.1		A0A3B3ISF6
KLHDC7B	ENST00000395676.4 linkuse as main transcript	c.208A>T	p.Thr70Ser	missense_variant	1/1	6		ENSP00000379034.2		Q96G42

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151620

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:

0.000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000951

AC:

AN:

157774

Hom.:

AF XY:

0.0000836

AC XY:

AN XY:

83756

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000903

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000236

AC:

AN:

1400122

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

690680

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:

0.00

Gnomad4 FIN exome

AF:

0.000658

Gnomad4 NFE exome

AF:

9.26e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151620

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

74036

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:

0.000945

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000195

AC:

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

Jun 16, 2023

The c.208A>T (p.T70S) alteration is located in exon 1 (coding exon 1) of the KLHDC7B gene. This alteration results from a A to T substitution at nucleotide position 208, causing the threonine (T) at amino acid position 70 to be replaced by a serine (S). 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

0.099

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.4

DANN

Benign

0.87

DEOGEN2

Benign

0.0045

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.21

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.0075

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

.;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.84

.;N

REVEL

Benign

0.10

Sift

Benign

0.36

.;T

Sift4G

Benign

0.63

.;T

Polyphen

0.010

.;B

Vest4

0.033

MutPred

0.097

.;Gain of relative solvent accessibility (P = 0.0479);

MVP

0.53

ClinPred

0.023

GERP RS

1.6

Varity_R

0.041

gMVP

0.081

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