6-73241569-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030568.5(KHDC1):ā€‹c.455T>Cā€‹(p.Ile152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

KHDC1
NM_030568.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.390
Variant links:
Genes affected
KHDC1 (HGNC:21366): (KH domain containing 1) Predicted to enable identical protein binding activity and poly(U) RNA binding activity. Predicted to be involved in activation of cysteine-type endopeptidase activity involved in apoptotic process. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1057502).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KHDC1NM_030568.5 linkc.455T>C p.Ile152Thr missense_variant 4/4 ENST00000257765.10 NP_085045.3 Q4VXA5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KHDC1ENST00000257765.10 linkc.455T>C p.Ile152Thr missense_variant 4/41 NM_030568.5 ENSP00000257765.5 Q4VXA5-2
KHDC1ENST00000370384.7 linkc.674T>C p.Ile225Thr missense_variant 5/51 ENSP00000359411.3 Q4VXA5-1
ENSG00000243501ENST00000423730.3 linkn.295+486T>C intron_variant 5 ENSP00000457270.2 F5H697

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461828
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727224
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:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 01, 2022The c.455T>C (p.I152T) alteration is located in exon 4 (coding exon 3) of the KHDC1 gene. This alteration results from a T to C substitution at nucleotide position 455, causing the isoleucine (I) at amino acid position 152 to be replaced by a threonine (T). 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
0.082
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
0.86
DANN
Benign
0.68
DEOGEN2
Benign
0.0010
.;T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.49
.;T;T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.11
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.55
.;N;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.99
N;N;.
REVEL
Benign
0.0060
Sift
Benign
0.049
D;.;.
Sift4G
Benign
0.20
T;T;T
Polyphen
0.054
.;B;.
Vest4
0.30
MutPred
0.46
.;Loss of sheet (P = 0.007);.;
MVP
0.014
MPC
0.061
ClinPred
0.042
T
GERP RS
-0.77
Varity_R
0.26
gMVP
0.0052

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: chr6-73951292; API