Variant 8-135645070-A-G 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.902A>G(p.Tyr301Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,613,454 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

KHDRBS3
NM_006558.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.73

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDRBS3	NM_006558.3 linkuse as main transcript	c.902A>G	p.Tyr301Cys	missense_variant	8/9	ENST00000355849.10	NP_006549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHDRBS3	ENST00000355849.10 linkuse as main transcript	c.902A>G	p.Tyr301Cys	missense_variant	8/9	1	NM_006558.3	ENSP00000348108	P1	O75525-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250548

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461274

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.0000378

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

Apr 12, 2024

The c.902A>G (p.Y301C) alteration is located in exon 8 (coding exon 8) of the KHDRBS3 gene. This alteration results from a A to G substitution at nucleotide position 902, causing the tyrosine (Y) at amino acid position 301 to be replaced by a cysteine (C). 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

0.23

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

1.0

D;.

Vest4

0.85

MutPred

0.34

Loss of phosphorylation at Y301 (P = 0.0182);.;

MVP

0.41

MPC

0.43

ClinPred

0.99

GERP RS

5.8

Varity_R

0.67

gMVP

0.71

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.

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