rs4696

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005340.7(HINT1):c.57T>C(p.Phe19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 1,612,466 control chromosomes in the GnomAD database, including 5,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2642 hom., cov: 33)

Exomes 𝑓: 0.038 ( 3094 hom. )

Consequence

HINT1
NM_005340.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.763

Variant links:

Genes affected

HINT1 (HGNC:4912): (histidine triad nucleotide binding protein 1) This gene encodes a protein that hydrolyzes purine nucleotide phosphoramidates substrates, including AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester, and AMP-NH2. The encoded protein interacts with these substrates via a histidine triad motif. This gene is considered a tumor suppressor gene. In addition, mutations in this gene can cause autosomal recessive neuromyotonia and axonal neuropathy. There are several related pseudogenes on chromosome 7. Several transcript variants have been observed. [provided by RefSeq, Dec 2015]

HINT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 5-131165149-A-G is Benign according to our data. Variant chr5-131165149-A-G is described in ClinVar as [Benign]. Clinvar id is 259745.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-131165149-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.763 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HINT1	NM_005340.7 linkuse as main transcript	c.57T>C	p.Phe19=	synonymous_variant	1/3	ENST00000304043.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HINT1	ENST00000304043.10 linkuse as main transcript	c.57T>C	p.Phe19=	synonymous_variant	1/3	1	NM_005340.7	P1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17954

AN:

152146

Hom.:

2639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.344

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0577

Gnomad ASJ

AF:

0.0882

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.00781

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0974

GnomAD3 exomes

AF:

0.0504

AC:

12571

AN:

249504

Hom.:

1144

AF XY:

0.0438

AC XY:

5913

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.0398

Gnomad ASJ exome

AF:

0.0905

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0153

Gnomad FIN exome

AF:

0.00843

Gnomad NFE exome

AF:

0.0325

Gnomad OTH exome

AF:

0.0568

GnomAD4 exome

AF:

0.0379

AC:

55399

AN:

1460202

Hom.:

3094

Cov.:

AF XY:

0.0368

AC XY:

26761

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.354

Gnomad4 AMR exome

AF:

0.0414

Gnomad4 ASJ exome

AF:

0.0855

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0162

Gnomad4 FIN exome

AF:

0.00998

Gnomad4 NFE exome

AF:

0.0302

Gnomad4 OTH exome

AF:

0.0544

GnomAD4 genome

AF:

0.118

AC:

17990

AN:

152264

Hom.:

2642

Cov.:

AF XY:

0.114

AC XY:

8462

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.344

Gnomad4 AMR

AF:

0.0576

Gnomad4 ASJ

AF:

0.0882

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0155

Gnomad4 FIN

AF:

0.00781

Gnomad4 NFE

AF:

0.0310

Gnomad4 OTH

AF:

0.0964

Alfa

AF:

0.0642

Hom.:

217

Bravo

AF:

0.133

Asia WGS

AF:

0.0300

AC:

104

AN:

3478

EpiCase

AF:

0.0371

EpiControl

AF:

0.0368

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal recessive axonal neuropathy with neuromyotonia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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