22-50548455-C-A

Variant summary

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

The NM_138433.5(KLHDC7B):​c.2212C>A​(p.Gln738Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KLHDC7B
NM_138433.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.576
Variant links:
Genes affected
KLHDC7B (HGNC:25145): (kelch domain containing 7B)

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=0.048483312).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KLHDC7BNM_138433.5 linkc.2212C>A p.Gln738Lys missense_variant 1/1 ENST00000648057.3 NP_612442.3 Q96G42

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KLHDC7BENST00000648057.3 linkc.2212C>A p.Gln738Lys missense_variant 1/1 NM_138433.5 ENSP00000497256.1 A0A3B3ISF6
KLHDC7BENST00000395676.4 linkc.289C>A p.Gln97Lys missense_variant 1/16 ENSP00000379034.2 Q96G42

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1427596
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
706652
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:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 GeneticsSep 08, 2024The c.289C>A (p.Q97K) alteration is located in exon 1 (coding exon 1) of the KLHDC7B gene. This alteration results from a C to A substitution at nucleotide position 289, causing the glutamine (Q) at amino acid position 97 to be replaced by a lysine (K). 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
0.079
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
0.13
DANN
Benign
0.55
DEOGEN2
Benign
0.0012
.;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.066
N
LIST_S2
Benign
0.34
T;T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.048
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.34
.;N
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.48
.;N
REVEL
Benign
0.032
Sift
Benign
1.0
.;T
Sift4G
Benign
0.84
.;T
Polyphen
0.017
.;B
Vest4
0.042
MutPred
0.37
.;Gain of solvent accessibility (P = 4e-04);
MVP
0.57
ClinPred
0.025
T
GERP RS
-3.2
Varity_R
0.056
gMVP
0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50986884; API