Variant 19-6415895-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366299.1(KHSRP):c.1600G>A(p.Ala534Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KHSRP
NM_001366299.1 missense, splice_region

Scores

Splicing: ADA: 0.001893

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.880

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13977039).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHSRP	NM_001366299.1 linkuse as main transcript	c.1600G>A	p.Ala534Thr	missense_variant, splice_region_variant	16/19	ENST00000600480.2	NP_001353228.1
KHSRP	NM_003685.3 linkuse as main transcript	c.1600G>A	p.Ala534Thr	missense_variant, splice_region_variant	16/20		NP_003676.2	Q92945
KHSRP	NM_001366300.1 linkuse as main transcript	c.1600G>A	p.Ala534Thr	missense_variant, splice_region_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.1600G>A	p.Ala534Thr	missense_variant, splice_region_variant	16/19	2	NM_001366299.1	ENSP00000471146.2	M0R0C6
KHSRP	ENST00000398148.7 linkuse as main transcript	c.1600G>A	p.Ala534Thr	missense_variant, splice_region_variant	16/20	1		ENSP00000381216.2	Q92945
KHSRP	ENST00000595223.5 linkuse as main transcript	c.346G>A	p.Ala116Thr	missense_variant, splice_region_variant	4/8	5		ENSP00000473254.1	M0R3J3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.35e-7

AC:

AN:

1360358

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

666678

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:

9.42e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 20, 2024

The c.1600G>A (p.A534T) alteration is located in exon 16 (coding exon 16) of the KHSRP gene. This alteration results from a G to A substitution at nucleotide position 1600, causing the alanine (A) at amino acid position 534 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

0.084

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.42

N;.

REVEL

Benign

0.040

Sift

Benign

0.41

T;.

Sift4G

Benign

0.62

T;T

Polyphen

0.0080

B;.

Vest4

0.25

MutPred

0.35

Gain of glycosylation at A534 (P = 0.0016);Gain of glycosylation at A534 (P = 0.0016);

MVP

0.54

MPC

1.1

ClinPred

0.24

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.074

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0019

dbscSNV1_RF

Benign

0.052

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over