Variant chr19-6421285-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001366299.1(KHSRP):c.418C>A(p.Pro140Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00128 in 1,588,980 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

KHSRP
NM_001366299.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

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:

KHSRP (HGNC:):

KHSRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05901581).

BS2

High AC in GnomAd4 at 109 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHSRP	NM_001366299.1 linkuse as main transcript	c.418C>A	p.Pro140Thr	missense_variant	4/19	ENST00000600480.2	NP_001353228.1
KHSRP	NM_003685.3 linkuse as main transcript	c.418C>A	p.Pro140Thr	missense_variant	4/20		NP_003676.2	Q92945
KHSRP	NM_001366300.1 linkuse as main transcript	c.418C>A	p.Pro140Thr	missense_variant	4/20		NP_001353229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHSRP	ENST00000600480.2 linkuse as main transcript	c.418C>A	p.Pro140Thr	missense_variant	4/19	2	NM_001366299.1	ENSP00000471146.2		M0R0C6

Frequencies

GnomAD3 genomes

AF:

0.000716

AC:

109

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000471

AC:

AN:

210274

Hom.:

AF XY:

0.000451

AC XY:

AN XY:

113094

show subpopulations

Gnomad AFR exome

AF:

0.0000816

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000155

Gnomad NFE exome

AF:

0.000976

Gnomad OTH exome

AF:

0.000748

GnomAD4 exome

AF:

0.00134

AC:

1923

AN:

1436742

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

878

AN XY:

712178

show subpopulations

Gnomad4 AFR exome

AF:

0.000242

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.000212

Gnomad4 NFE exome

AF:

0.00161

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.000716

AC:

109

AN:

152238

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.000623

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000257

AC:

ESP6500EA

AF:

0.000725

AC:

ExAC

AF:

0.000282

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Feb 12, 2024

The c.418C>A (p.P140T) alteration is located in exon 4 (coding exon 4) of the KHSRP gene. This alteration results from a C to A substitution at nucleotide position 418, causing the proline (P) at amino acid position 140 to be replaced by a threonine (T). 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

0.068

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

-0.091

Eigen_PC

Benign

0.086

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.059

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

0.86

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.063

Sift

Benign

0.44

T;.

Sift4G

Benign

0.48

T;T

Polyphen

0.0010

B;.

Vest4

0.46

MVP

0.55

MPC

1.2

ClinPred

0.032

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.37

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