1-32014108-C-T

Variant summary

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

The NM_006559.3(KHDRBS1):​c.113C>T​(p.Pro38Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

KHDRBS1
NM_006559.3 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73
Variant links:
Genes affected
KHDRBS1 (HGNC:18116): (KH RNA binding domain containing, signal transduction associated 1) This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated protein family. The encoded protein appears to have many functions and may be involved in a variety of cellular processes, including alternative splicing, cell cycle regulation, RNA 3'-end formation, tumorigenesis, and regulation of human immunodeficiency virus gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

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=0.19695291).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KHDRBS1NM_006559.3 linkuse as main transcriptc.113C>T p.Pro38Leu missense_variant 1/9 ENST00000327300.12 NP_006550.1 Q07666-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KHDRBS1ENST00000327300.12 linkuse as main transcriptc.113C>T p.Pro38Leu missense_variant 1/91 NM_006559.3 ENSP00000313829.7 Q07666-1
KHDRBS1ENST00000492989.1 linkuse as main transcriptc.113C>T p.Pro38Leu missense_variant 1/81 ENSP00000417731.1 Q07666-3
KHDRBS1ENST00000307714.12 linkuse as main transcriptn.183C>T non_coding_transcript_exon_variant 1/91

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1279304
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
629536
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.:
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 19, 2023The c.113C>T (p.P38L) alteration is located in exon 1 (coding exon 1) of the KHDRBS1 gene. This alteration results from a C to T substitution at nucleotide position 113, causing the proline (P) at amino acid position 38 to be replaced by a leucine (L). 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
0.088
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.83
T;T
M_CAP
Pathogenic
0.77
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.72
N;N
REVEL
Benign
0.037
Sift
Uncertain
0.014
D;D
Sift4G
Benign
0.68
T;T
Polyphen
0.47
P;B
Vest4
0.22
MutPred
0.18
Loss of glycosylation at P38 (P = 0.0351);Loss of glycosylation at P38 (P = 0.0351);
MVP
0.46
MPC
1.1
ClinPred
0.54
D
GERP RS
4.0
Varity_R
0.14
gMVP
0.38

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: chr1-32479709; API