6-125957062-G-T

Variant names:

• chr6-125957062-G-T
• rs147213100
• NM_138571.5:c.85G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138571.5(HINT3):​c.85G>T​(p.Val29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V29M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: HINT3 NM_138571.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 0 publications found

Genes affected

HINT3 (HGNC:18468): (histidine triad nucleotide binding protein 3) Histidine triad proteins, such as HINT3, are nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides (Brenner, 2002 [PubMed 12119013]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044094205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HINT3	NM_138571.5	c.85G>T	p.Val29Leu	missense_variant	Exon 1 of 5	ENST00000229633.7	NP_612638.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HINT3	ENST00000229633.7	c.85G>T	p.Val29Leu	missense_variant	Exon 1 of 5	1	NM_138571.5	ENSP00000229633.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398480 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 689788

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078826

Other (OTH) AF: 0.00 AC: 0 AN: 57978

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.013
DANN	Benign	0.37
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.13
Sift	Benign	0.87	T
Sift4G	Benign	0.47	T
Polyphen		0.017	B
Vest4		0.036
MutPred		0.21		Loss of loop (P = 0.0203);
MVP		0.68
MPC		0.056
ClinPred		0.064	T
GERP RS		-7.2
PromoterAI		0.054	Neutral
Varity_R		0.074
gMVP		0.19
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs147213100; hg19: chr6-126278208;