Variant 9-35813280-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032593.3(HINT2):c.386A>T(p.Asp129Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HINT2
NM_032593.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

Variant links:

Genes affected

HINT2 (HGNC:18344): (histidine triad nucleotide binding protein 2) Histidine triad proteins, such as HINT2, are nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides (Brenner, 2002 [PubMed 12119013]).[supplied by OMIM, Mar 2008]

HINT2 links:

HINT2 (HGNC:):

HINT2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HINT2	NM_032593.3 linkuse as main transcript	c.386A>T	p.Asp129Val	missense_variant	4/5	ENST00000259667.6	NP_115982.1	Q9BX68
HINT2	XM_024447702.2 linkuse as main transcript	c.392A>T	p.Asp131Val	missense_variant	4/5		XP_024303470.1
HINT2	XM_024447703.1 linkuse as main transcript	c.392A>T	p.Asp131Val	missense_variant	4/5		XP_024303471.1
HINT2	XM_024447704.2 linkuse as main transcript	c.386A>T	p.Asp129Val	missense_variant	4/5		XP_024303472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HINT2	ENST00000259667.6 linkuse as main transcript	c.386A>T	p.Asp129Val	missense_variant	4/5	1	NM_032593.3	ENSP00000259667.5	Q9BX68
ENSG00000285645	ENST00000650284.1 linkuse as main transcript	n.*860A>T		non_coding_transcript_exon_variant	9/10			ENSP00000498023.1	A0A3B3IU11
ENSG00000285645	ENST00000650284.1 linkuse as main transcript	n.*860A>T		3_prime_UTR_variant	9/10			ENSP00000498023.1	A0A3B3IU11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251444

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461644

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

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

Cov.:

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

Oct 03, 2024

The c.386A>T (p.D129V) alteration is located in exon 4 (coding exon 4) of the HINT2 gene. This alteration results from a A to T substitution at nucleotide position 386, causing the aspartic acid (D) at amino acid position 129 to be replaced by a valine (V). 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

0.29

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.62

MetaRNN

Pathogenic

0.88

MetaSVM

Pathogenic

0.92

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.84

Sift

Uncertain

0.021

Sift4G

Uncertain

0.0090

Polyphen

0.94

Vest4

0.54

MutPred

0.54

Loss of disorder (P = 0.0636);

MVP

0.99

MPC

0.46

ClinPred

0.99

GERP RS

4.6

Varity_R

0.80

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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