chr1-155921567-A-T

Variant summary

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

The ENST00000368321.8(KHDC4):​c.1074T>A​(p.Asn358Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,461,836 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N358S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

KHDC4
ENST00000368321.8 missense

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77
Variant links:
Genes affected
KHDC4 (HGNC:29145): (KH domain containing 4, pre-mRNA splicing factor) Enables RNA binding activity. Involved in mRNA splice site selection. Located in cytoplasm and nucleoplasm. Colocalizes with spliceosomal 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=0.21772686).
BS2
High AC in GnomAdExome4 at 39 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KHDC4NM_014949.4 linkuse as main transcriptc.1074T>A p.Asn358Lys missense_variant 10/14 ENST00000368321.8 NP_055764.2 Q7Z7F0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KHDC4ENST00000368321.8 linkuse as main transcriptc.1074T>A p.Asn358Lys missense_variant 10/141 NM_014949.4 ENSP00000357304.3 Q7Z7F0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461836
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
12
AN XY:
727218
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:
0.0000351
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 GeneticsJan 10, 2022The c.1074T>A (p.N358K) alteration is located in exon 10 (coding exon 10) of the KIAA0907 gene. This alteration results from a T to A substitution at nucleotide position 1074, causing the asparagine (N) at amino acid position 358 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
Pathogenic
0.64
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.058
T;.
Eigen
Benign
-0.19
Eigen_PC
Benign
0.016
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.7
N;N
REVEL
Benign
0.041
Sift
Benign
0.064
T;T
Sift4G
Benign
0.93
T;T
Polyphen
0.0040
B;B
Vest4
0.57
MutPred
0.26
Gain of methylation at N358 (P = 0.0023);Gain of methylation at N358 (P = 0.0023);
MVP
0.16
MPC
0.56
ClinPred
0.57
D
GERP RS
4.5
Varity_R
0.14
gMVP
0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155891358; API