Variant 19-6415858-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366299.1(KHSRP):c.1637G>C(p.Gly546Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000263 in 152,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KHSRP
NM_001366299.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHSRP	NM_001366299.1 linkuse as main transcript	c.1637G>C	p.Gly546Ala	missense_variant	16/19	ENST00000600480.2	NP_001353228.1
KHSRP	NM_003685.3 linkuse as main transcript	c.1637G>C	p.Gly546Ala	missense_variant	16/20		NP_003676.2	Q92945
KHSRP	NM_001366300.1 linkuse as main transcript	c.1637G>C	p.Gly546Ala	missense_variant	16/20		NP_001353229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KHSRP	ENST00000600480.2 linkuse as main transcript	c.1637G>C	p.Gly546Ala	missense_variant	16/19	2	NM_001366299.1	ENSP00000471146.2	M0R0C6
KHSRP	ENST00000398148.7 linkuse as main transcript	c.1637G>C	p.Gly546Ala	missense_variant	16/20	1		ENSP00000381216.2	Q92945
KHSRP	ENST00000595223.5 linkuse as main transcript	c.383G>C	p.Gly128Ala	missense_variant	4/8	5		ENSP00000473254.1	M0R3J3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1415000

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699152

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.0000966

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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

Dec 19, 2022

The c.1637G>C (p.G546A) alteration is located in exon 16 (coding exon 16) of the KHSRP gene. This alteration results from a G to C substitution at nucleotide position 1637, causing the glycine (G) at amino acid position 546 to be replaced by an alanine (A). 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

Uncertain

0.070

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

D;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.46

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.8

L;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.8

D;.

REVEL

Benign

0.25

Sift

Benign

0.054

T;.

Sift4G

Uncertain

0.060

T;T

Polyphen

1.0

D;.

Vest4

0.57

MutPred

0.25

Gain of catalytic residue at G546 (P = 0.084);Gain of catalytic residue at G546 (P = 0.084);

MVP

0.66

MPC

2.2

ClinPred

0.98

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.58

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