1-32014295-G-T

Variant summary

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

The NM_006559.3(KHDRBS1):​c.300G>T​(p.Glu100Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

KHDRBS1
NM_006559.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93
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=0.10493189).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KHDRBS1NM_006559.3 linkc.300G>T p.Glu100Asp 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 linkc.300G>T p.Glu100Asp missense_variant 1/91 NM_006559.3 ENSP00000313829.7 Q07666-1
KHDRBS1ENST00000492989.1 linkc.300G>T p.Glu100Asp missense_variant 1/81 ENSP00000417731.1 Q07666-3
KHDRBS1ENST00000307714.12 linkn.370G>T non_coding_transcript_exon_variant 1/91
KHDRBS1ENST00000484270.2 linkn.114G>T non_coding_transcript_exon_variant 1/115

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.10e-7
AC:
1
AN:
1408960
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
697708
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000283
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
Bravo
AF:
0.00000378

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 GeneticsMar 22, 2023The c.300G>T (p.E100D) alteration is located in exon 1 (coding exon 1) of the KHDRBS1 gene. This alteration results from a G to T substitution at nucleotide position 300, causing the glutamic acid (E) at amino acid position 100 to be replaced by an aspartic acid (D). 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
0.14
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T;.
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.82
T;T
M_CAP
Uncertain
0.089
D
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.31
N;N
REVEL
Benign
0.025
Sift
Benign
0.23
T;T
Sift4G
Benign
0.44
T;T
Polyphen
0.0080
B;B
Vest4
0.21
MutPred
0.19
Loss of methylation at K102 (P = 0.0956);Loss of methylation at K102 (P = 0.0956);
MVP
0.44
MPC
0.91
ClinPred
0.61
D
GERP RS
3.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs755592365; hg19: chr1-32479896; API