Variant 8-135645081-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006558.3(KHDRBS3):c.913G>A(p.Gly305Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000534 in 1,613,308 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00055 ( 1 hom. )

Consequence

KHDRBS3
NM_006558.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.71

Variant links:

Genes affected

KHDRBS3 (HGNC:18117): (KH RNA binding domain containing, signal transduction associated 3) Enables RNA binding activity; identical protein binding activity; and protein domain specific binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome and spermatogenesis. Located in nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

KHDRBS3 links:

KHDRBS3 (HGNC:):

KHDRBS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 58 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDRBS3	NM_006558.3 linkuse as main transcript	c.913G>A	p.Gly305Arg	missense_variant	8/9	ENST00000355849.10	NP_006549.1	O75525-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHDRBS3	ENST00000355849.10 linkuse as main transcript	c.913G>A	p.Gly305Arg	missense_variant	8/9	1	NM_006558.3	ENSP00000348108.5		O75525-1

Frequencies

GnomAD3 genomes

AF:

0.000382

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000351

AC:

AN:

250548

Hom.:

AF XY:

0.000369

AC XY:

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000592

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000550

AC:

804

AN:

1461344

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

407

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.000653

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000382

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.000218

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000441

Hom.:

Bravo

AF:

0.000336

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

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

Jun 13, 2022

The c.913G>A (p.G305R) alteration is located in exon 8 (coding exon 8) of the KHDRBS3 gene. This alteration results from a G to A substitution at nucleotide position 913, causing the glycine (G) at amino acid position 305 to be replaced by an arginine (R). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.075

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.0080

D;T

Polyphen

1.0

D;.

Vest4

0.76

MutPred

0.45

Gain of solvent accessibility (P = 0.0055);.;

MVP

0.42

MPC

0.34

ClinPred

0.69

GERP RS

5.8

Varity_R

0.47

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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