Genetic Variant NM_138433.5:c.2447A>C (chr22-50548690-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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

Publications

0 publications found

Variant links:

Genes affected

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

KLHDC7B links:

KLHDC7B-DT (HGNC:53791): (KLHDC7B divergent transcript)

KLHDC7B-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106710404).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138433.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC7B	NM_138433.5	MANE Select	c.2447A>C	p.Lys816Thr	missense	Exon 1 of 1	NP_612442.3	A0A3B3ISF6
	KLHDC7B-DT	NR_199716.1		n.52+206T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLHDC7B	ENST00000648057.3	MANE Select	c.2447A>C	p.Lys816Thr	missense	Exon 1 of 1	ENSP00000497256.1	A0A3B3ISF6
KLHDC7B-DT	ENST00000796180.1		n.126T>G		non_coding_transcript_exon	Exon 1 of 4
KLHDC7B-DT	ENST00000796181.1		n.34T>G		non_coding_transcript_exon	Exon 1 of 5

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

African (AFR)

AF:

0.0000341

AC:

AN:

29318

American (AMR)

AF:

0.00

AC:

AN:

31834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22616

East Asian (EAS)

AF:

0.00

AC:

AN:

34894

South Asian (SAS)

AF:

0.00

AC:

AN:

75556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4794

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066786

Other (OTH)

AF:

0.00

AC:

AN:

56348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151742

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74110

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41318

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67874

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.2

PhyloP100

0.50

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.8

REVEL

Benign

0.28

Sift

Benign

0.054

Sift4G

Benign

0.27

Polyphen

0.60

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

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over