HINT1 p.His110His

Variant names:

• chr5-131159497-C-C
• NM_005340.7:c.

Your query was ambiguous. Multiple possible variants found:

• chr5-131159498--
• chr5-131159498-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005340.7(HINT1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HINT1 NM_005340.7 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Gamstorp-Wohlfart syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005340.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HINT1	NM_005340.7	MANE Select	c.		exon_region	Exon 3 of 3	NP_005331.1	P49773
	HINT1	NM_001437949.1		c.		exon_region	Exon 3 of 3	NP_001424878.1	D6RD60
	HINT1	NM_001437950.1		c.		exon_region	Exon 2 of 2	NP_001424879.1	D6RE99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HINT1	ENST00000304043.10	TSL:1 MANE Select	c.		exon_region	Exon 3 of 3	ENSP00000304229.5	P49773
	HINT1	ENST00000508495.5	TSL:1	n.		exon_region	Exon 4 of 4	ENSP00000424974.1	D6REP8
	HINT1	ENST00000508495.5	TSL:1	n.		3_prime_UTR	Exon 4 of 4	ENSP00000424974.1	D6REP8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.061

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-130495190;