6-73242170-C-A

Variant summary

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

The NM_030568.5(KHDC1):​c.180G>T​(p.Trp60Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

KHDC1
NM_030568.5 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.452
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=0.16056415).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KHDC1NM_030568.5 linkc.180G>T p.Trp60Cys missense_variant 3/4 ENST00000257765.10 NP_085045.3 Q4VXA5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KHDC1ENST00000257765.10 linkc.180G>T p.Trp60Cys missense_variant 3/41 NM_030568.5 ENSP00000257765.5 Q4VXA5-2
KHDC1ENST00000370384.7 linkc.399G>T p.Trp133Cys missense_variant 4/51 ENSP00000359411.3 Q4VXA5-1
ENSG00000243501ENST00000423730.3 linkn.180G>T non_coding_transcript_exon_variant 3/85 ENSP00000457270.2 F5H697
KHDC1ENST00000433730.1 linkc.180G>T p.Trp60Cys missense_variant 3/33 ENSP00000406966.1 A6PVU5

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000642
AC:
16
AN:
249294
Hom.:
0
AF XY:
0.0000813
AC XY:
11
AN XY:
135254
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000496
GnomAD4 exome
AF:
0.0000636
AC:
93
AN:
1461866
Hom.:
0
Cov.:
32
AF XY:
0.0000550
AC XY:
40
AN XY:
727230
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:
0.0000562
Gnomad4 NFE exome
AF:
0.0000746
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000118
AC:
1
ExAC
AF:
0.0000744
AC:
9
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 GeneticsNov 15, 2021The c.180G>T (p.W60C) alteration is located in exon 3 (coding exon 2) of the KHDC1 gene. This alteration results from a G to T substitution at nucleotide position 180, causing the tryptophan (W) at amino acid position 60 to be replaced by a cysteine (C). 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
Uncertain
0.51
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
18
DANN
Benign
0.88
DEOGEN2
Benign
0.045
.;T;.;.;.
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.0053
N
LIST_S2
Benign
0.59
.;T;T;T;T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.16
T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.75
.;N;.;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-10
D;D;.;.;D
REVEL
Benign
0.20
Sift
Benign
0.10
T;.;.;.;T
Sift4G
Benign
0.15
T;T;T;T;.
Polyphen
0.0080
.;B;.;.;.
Vest4
0.42
MutPred
0.65
.;Loss of helix (P = 0.0626);.;.;.;
MVP
0.040
MPC
0.063
ClinPred
0.064
T
GERP RS
1.0
Varity_R
0.78
gMVP
0.063

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs369480492; hg19: chr6-73951893; API