Variant 19-6415160-G-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.2108C>T(p.Thr703Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000688 in 1,454,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

KHSRP
NM_001366299.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

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=0.1539191).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KHSRP	NM_001366299.1 linkuse as main transcript	c.2108C>T	p.Thr703Met	missense_variant	19/19	ENST00000600480.2	NP_001353228.1
KHSRP	NM_003685.3 linkuse as main transcript	c.2108C>T	p.Thr703Met	missense_variant	19/20		NP_003676.2
KHSRP	NM_001366300.1 linkuse as main transcript	c.2033C>T	p.Thr678Met	missense_variant	19/20		NP_001353229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHSRP	ENST00000600480.2 linkuse as main transcript	c.2108C>T	p.Thr703Met	missense_variant	19/19	2	NM_001366299.1	ENSP00000471146	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

239590

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131296

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000555

Gnomad NFE exome

AF:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000688

AC:

AN:

1454332

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000414

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

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

Nov 17, 2022

The c.2108C>T (p.T703M) alteration is located in exon 19 (coding exon 19) of the KHSRP gene. This alteration results from a C to T substitution at nucleotide position 2108, causing the threonine (T) at amino acid position 703 to be replaced by a methionine (M). 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

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

0.043

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.71

N;.

REVEL

Benign

0.15

Sift

Uncertain

0.011

D;.

Sift4G

Uncertain

0.054

T;D

Polyphen

0.61

P;.

Vest4

0.30

MutPred

0.11

Loss of phosphorylation at T703 (P = 0.0037);.;

MVP

0.44

MPC

1.1

ClinPred

0.28

GERP RS

4.5

Varity_R

0.15

gMVP

0.13

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