chr7-130070728-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014997.4(KLHDC10):ā€‹c.85G>Cā€‹(p.Gly29Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,279,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000015 ( 0 hom. )

Consequence

KLHDC10
NM_014997.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.00
Variant links:
Genes affected
KLHDC10 (HGNC:22194): (kelch domain containing 10) Enables ubiquitin ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in nucleoplasm. Is active in Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14274973).
BS2
High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLHDC10NM_014997.4 linkuse as main transcriptc.85G>C p.Gly29Arg missense_variant 1/10 ENST00000335420.10 NP_055812.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLHDC10ENST00000335420.10 linkuse as main transcriptc.85G>C p.Gly29Arg missense_variant 1/101 NM_014997.4 ENSP00000334140 P1Q6PID8-1
KLHDC10ENST00000463413.1 linkuse as main transcriptc.85G>C p.Gly29Arg missense_variant 1/32 ENSP00000420083
KLHDC10ENST00000468226.1 linkuse as main transcript upstream_gene_variant 3 ENSP00000420034

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000151
AC:
17
AN:
1127820
Hom.:
0
Cov.:
33
AF XY:
0.0000204
AC XY:
11
AN XY:
540426
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000109
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000285
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000138
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340

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 submitterclinical testingAmbry GeneticsDec 16, 2021The c.85G>C (p.G29R) alteration is located in exon 1 (coding exon 1) of the KLHDC10 gene. This alteration results from a G to C substitution at nucleotide position 85, causing the glycine (G) at amino acid position 29 to be replaced by an arginine (R). 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
0.33
BayesDel_addAF
Benign
-0.045
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T;T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.065
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.62
T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;.
MutationTaster
Benign
0.95
N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
0.30
N;N
REVEL
Benign
0.084
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.019
D;D
Polyphen
0.0
B;.
Vest4
0.38
MutPred
0.35
Gain of methylation at G29 (P = 7e-04);Gain of methylation at G29 (P = 7e-04);
MVP
0.093
MPC
1.4
ClinPred
0.87
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6
Varity_R
0.25
gMVP
0.41

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.

Other links and lift over

dbSNP: rs1037010334; hg19: chr7-129710568; API