Variant 1-32014033-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006559.3(KHDRBS1):c.38G>C(p.Arg13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,374,490 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 (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

KHDRBS1
NM_006559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

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]

KHDRBS1 links:

KHDRBS1 (HGNC:):

KHDRBS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34137034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDRBS1	NM_006559.3 linkuse as main transcript	c.38G>C	p.Arg13Pro	missense_variant	1/9	ENST00000327300.12	NP_006550.1	Q07666-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KHDRBS1	ENST00000327300.12 linkuse as main transcript	c.38G>C	p.Arg13Pro	missense_variant	1/9	1	NM_006559.3	ENSP00000313829.7	Q07666-1
KHDRBS1	ENST00000492989.1 linkuse as main transcript	c.38G>C	p.Arg13Pro	missense_variant	1/8	1		ENSP00000417731.1	Q07666-3
KHDRBS1	ENST00000307714.12 linkuse as main transcript	n.108G>C		non_coding_transcript_exon_variant	1/9	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.28e-7

AC:

AN:

1374490

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

682834

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:

9.25e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.38G>C (p.R13P) alteration is located in exon 1 (coding exon 1) of the KHDRBS1 gene. This alteration results from a G to C substitution at nucleotide position 38, causing the arginine (R) at amino acid position 13 to be replaced by a proline (P). 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

0.13

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

0.031

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

T;T

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.57

P;P

Vest4

0.36

MutPred

0.24

Loss of MoRF binding (P = 0.013);Loss of MoRF binding (P = 0.013);

MVP

0.88

MPC

2.3

ClinPred

0.58

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.42

gMVP

0.51

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over