16-728330-C-T

Variant names:

• chr16-728330-C-T
• rs756866510
• NM_032304.4:c.303C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_032304.4(HAGHL):​c.303C>T​(p.His101His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,409,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: HAGHL NM_032304.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 0 publications found

Genes affected

HAGHL (HGNC:14177): (hydroxyacylglutathione hydrolase like) Predicted to enable hydroxyacylglutathione hydrolase activity and metal ion binding activity. Predicted to be involved in methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.071).
• BP7: Synonymous conserved (PhyloP=-0.21 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032304.4. 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
	HAGHL	NM_032304.4	MANE Select	c.303C>T	p.His101His	synonymous	Exon 4 of 8	NP_115680.1	Q6PII5-2
	HAGHL	NM_001323636.2		c.303C>T	p.His101His	synonymous	Exon 5 of 8	NP_001310565.1
	HAGHL	NM_207112.2		c.303C>T	p.His101His	synonymous	Exon 5 of 7	NP_996995.1	Q6PII5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAGHL	ENST00000389703.8	TSL:1 MANE Select	c.303C>T	p.His101His	synonymous	Exon 4 of 8	ENSP00000374353.3	Q6PII5-2
	HAGHL	ENST00000389701.9	TSL:1	n.490C>T		non_coding_transcript_exon	Exon 3 of 7
	HAGHL	ENST00000341413.8	TSL:2	c.303C>T	p.His101His	synonymous	Exon 5 of 7	ENSP00000341952.4	Q6PII5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1409044 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 697846

African (AFR) AF: 0.00 AC: 0 AN: 31832

American (AMR) AF: 0.00 AC: 0 AN: 39126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 37238

South Asian (SAS) AF: 0.00 AC: 0 AN: 80746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1089958

Other (OTH) AF: 0.00 AC: 0 AN: 58520

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.97
PhyloP100		-0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs756866510; hg19: chr16-778330;