chr5-131161735-T-C

Position:

• chr5-131161735-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005340.7(HINT1):​c.216+837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,152 control chromosomes in the GnomAD database, including 14,275 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (14275 hom., cov: 32)
• Consequence: HINT1 NM_005340.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HINT1	NM_005340.7	c.216+837A>G		intron_variant		ENST00000304043.10	NP_005331.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HINT1	ENST00000304043.10	c.216+837A>G		intron_variant		1	NM_005340.7	ENSP00000304229	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58156 AN: 152032 Hom.: 14242 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.383 AC: 58225 AN: 152152 Hom.: 14275 Cov.: 32 AF XY: 0.378 AC XY: 28113 AN XY: 74388

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.349

Alfa AF: 0.279 Hom.: 3638

Bravo AF: 0.392

Asia WGS AF: 0.321 AC: 1117 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.73
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs3864283; hg19: chr5-130497428;