Variant 19-6424617-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001366299.1(KHSRP):c.85G>T(p.Gly29Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 971,492 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: 𝑓 0.000078 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

KHSRP
NM_001366299.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

KHSRP (HGNC:6316): (KH-type splicing regulatory protein) The KHSRP gene encodes a multifunctional RNA-binding protein implicated in a variety of cellular processes, including transcription, alternative pre-mRNA splicing, and mRNA localization (Min et al., 1997 [PubMed 9136930]; Gherzi et al., 2004 [PubMed 15175153]).[supplied by OMIM, Apr 2010]

KHSRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17200226).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KHSRP	NM_001366299.1 linkuse as main transcript	c.85G>T	p.Gly29Cys	missense_variant	1/19	ENST00000600480.2	NP_001353228.1
KHSRP	NM_003685.3 linkuse as main transcript	c.85G>T	p.Gly29Cys	missense_variant	1/20		NP_003676.2
KHSRP	NM_001366300.1 linkuse as main transcript	c.85G>T	p.Gly29Cys	missense_variant	1/20		NP_001353229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHSRP	ENST00000600480.2 linkuse as main transcript	c.85G>T	p.Gly29Cys	missense_variant	1/19	2	NM_001366299.1	ENSP00000471146	A2
KHSRP	ENST00000398148.7 linkuse as main transcript	c.85G>T	p.Gly29Cys	missense_variant	1/20	1		ENSP00000381216	P2

Frequencies

GnomAD3 genomes

AF:

0.0000775

AC:

AN:

141874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000251

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:

0.000156

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000135

AC:

112

AN:

829618

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

383838

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:

0.000147

Gnomad4 OTH exome

AF:

0.0000366

GnomAD4 genome

AF:

0.0000775

AC:

AN:

141874

Hom.:

Cov.:

AF XY:

0.0000726

AC XY:

AN XY:

68842

show subpopulations

Gnomad4 AFR

AF:

0.0000251

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:

0.000156

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000642

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

Aug 22, 2023

The c.85G>T (p.G29C) alteration is located in exon 1 (coding exon 1) of the KHSRP gene. This alteration results from a G to T substitution at nucleotide position 85, causing the glycine (G) at amino acid position 29 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.0059

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.49

T;T

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.33

N;.

REVEL

Benign

0.062

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.028

D;D

Polyphen

0.84

P;.

Vest4

0.26

MutPred

0.42

Loss of glycosylation at P34 (P = 0.2356);Loss of glycosylation at P34 (P = 0.2356);

MVP

0.47

MPC

1.1

ClinPred

0.51

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.22

gMVP

0.35

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