9-35813454-T-G

Position:

chr9-35813454-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032593.3(HINT2):c.318A>C(p.Glu106Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

HINT2
NM_032593.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.09

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008765459).

BP6

Variant 9-35813454-T-G is Benign according to our data. Variant chr9-35813454-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3105866.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HINT2	NM_032593.3 linkuse as main transcript	c.318A>C	p.Glu106Asp	missense_variant	3/5	ENST00000259667.6	NP_115982.1	Q9BX68
HINT2	XM_024447702.2 linkuse as main transcript	c.324A>C	p.Glu108Asp	missense_variant	3/5		XP_024303470.1
HINT2	XM_024447703.1 linkuse as main transcript	c.324A>C	p.Glu108Asp	missense_variant	3/5		XP_024303471.1
HINT2	XM_024447704.2 linkuse as main transcript	c.318A>C	p.Glu106Asp	missense_variant	3/5		XP_024303472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HINT2	ENST00000259667.6 linkuse as main transcript	c.318A>C	p.Glu106Asp	missense_variant	3/5	1	NM_032593.3	ENSP00000259667.5	Q9BX68
ENSG00000285645	ENST00000650284.1 linkuse as main transcript	n.*792A>C		non_coding_transcript_exon_variant	8/10			ENSP00000498023.1	A0A3B3IU11
ENSG00000285645	ENST00000650284.1 linkuse as main transcript	n.*792A>C		3_prime_UTR_variant	8/10			ENSP00000498023.1	A0A3B3IU11

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251418

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000978

AC:

143

AN:

1461742

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00333

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000138

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.7

DANN

Benign

0.81

DEOGEN2

Benign

0.36

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.72

M_CAP

Benign

0.013

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.30

REVEL

Benign

0.13

Sift

Benign

0.49

Sift4G

Benign

0.55

Polyphen

0.0010

Vest4

0.23

MutPred

0.44

Gain of relative solvent accessibility (P = 0.1684);

MVP

0.41

MPC

0.15

ClinPred

0.012

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.24

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