dbSNP rs11576830: KLHDC9:p.Ser171Arg (chr1-161099046-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152366.5(KLHDC9):c.511A>C(p.Ser171Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,595,180 control chromosomes in the GnomAD database, including 67,436 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.24 ( 5124 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62312 hom. )

Consequence

KLHDC9
NM_152366.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Variant links:

Genes affected

KLHDC9 (HGNC:28489): (kelch domain containing 9) Enables cyclin binding activity. [provided by Alliance of Genome Resources, Apr 2022]

KLHDC9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029716194).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC9	NM_152366.5 link	c.511A>C	p.Ser171Arg	missense_variant	Exon 1 of 4	ENST00000368011.9	NP_689579.3	Q8NEP7-1
KLHDC9	NM_001007255.3 link	c.511A>C	p.Ser171Arg	missense_variant	Exon 1 of 4		NP_001007256.1	Q8NEP7-2
KLHDC9	NR_033385.2 link	n.425A>C		non_coding_transcript_exon_variant	Exon 2 of 5
KLHDC9	NR_033386.2 link	n.425A>C		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC9	ENST00000368011.9 link	c.511A>C	p.Ser171Arg	missense_variant	Exon 1 of 4	1	NM_152366.5	ENSP00000356990.4		Q8NEP7-1

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36738

AN:

152016

Hom.:

5126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0980

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.275

AC:

62139

AN:

225880

Hom.:

8876

AF XY:

0.273

AC XY:

33939

AN XY:

124352

show subpopulations

Gnomad AFR exome

AF:

0.0881

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.347

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.312

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.291

AC:

420082

AN:

1443046

Hom.:

62312

Cov.:

AF XY:

0.289

AC XY:

207233

AN XY:

718026

show subpopulations

Gnomad4 AFR exome

AF:

0.0858

Gnomad4 AMR exome

AF:

0.309

Gnomad4 ASJ exome

AF:

0.278

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.277

GnomAD4 genome

AF:

0.242

AC:

36750

AN:

152134

Hom.:

5124

Cov.:

AF XY:

0.243

AC XY:

18053

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0982

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.365

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.280

Hom.:

10101

Bravo

AF:

0.236

TwinsUK

AF:

0.292

AC:

1081

ALSPAC

AF:

0.284

AC:

1094

ESP6500AA

AF:

0.0927

AC:

407

ESP6500EA

AF:

0.282

AC:

2416

ExAC

AF:

0.262

AC:

31660

Asia WGS

AF:

0.258

AC:

897

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.3

DANN

Benign

0.56

DEOGEN2

Benign

0.0047

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.60

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.052

Sift

Benign

0.52

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.0

B;B

Vest4

0.17

MutPred

0.22

Gain of MoRF binding (P = 0.0164);Gain of MoRF binding (P = 0.0164);

MPC

0.34

ClinPred

0.0034

GERP RS

-7.1

Varity_R

0.042

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over