Variant 1-32037875-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000327300.12(KHDRBS1):c.946G>A(p.Gly316Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KHDRBS1
ENST00000327300.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.71

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDRBS1	NM_006559.3 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	6/9	ENST00000327300.12	NP_006550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHDRBS1	ENST00000327300.12 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	6/9	1	NM_006559.3	ENSP00000313829	P1	Q07666-1
KHDRBS1	ENST00000492989.1 linkuse as main transcript	c.829G>A	p.Gly277Ser	missense_variant	5/8	1		ENSP00000417731		Q07666-3
KHDRBS1	ENST00000307714.12 linkuse as main transcript	n.1016G>A		non_coding_transcript_exon_variant	6/9	1
KHDRBS1	ENST00000484270.2 linkuse as main transcript	n.760G>A		non_coding_transcript_exon_variant	6/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251322

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jul 12, 2023

The c.946G>A (p.G316S) alteration is located in exon 6 (coding exon 6) of the KHDRBS1 gene. This alteration results from a G to A substitution at nucleotide position 946, causing the glycine (G) at amino acid position 316 to be replaced by a serine (S). 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

0.17

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.18

Sift

Benign

0.28

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.19

B;B

Vest4

0.88

MutPred

0.28

Gain of glycosylation at G316 (P = 0.0065);.;

MVP

0.74

MPC

2.1

ClinPred

0.92

GERP RS

4.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.34

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over