16-729027-G-T

Variant names:

• chr16-729027-G-T
• rs369303595
• NM_032304.4:c.619G>T

Variant summary

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

The NM_032304.4(HAGHL):​c.619G>T​(p.Val207Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. V207M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HAGHL NM_032304.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025052369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAGHL	NM_032304.4	c.619G>T	p.Val207Leu	missense_variant	Exon 7 of 8	ENST00000389703.8	NP_115680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAGHL	ENST00000389703.8	c.619G>T	p.Val207Leu	missense_variant	Exon 7 of 8	1	NM_032304.4	ENSP00000374353.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457428 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724824

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39584

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111202

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.4
DANN	Benign	0.72
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.30	T;T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.025	T;T
MetaSVM	Benign	-0.50	T
PhyloP100		-0.60
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.18
Sift	Benign	0.38	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0	B;B
Vest4		0.089
MutPred		0.19		Gain of disorder (P = 0.1885);Gain of disorder (P = 0.1885);
MVP		0.31
MPC		0.19
ClinPred		0.012	T
GERP RS		-2.6
gMVP		0.22
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: rs369303595; hg19: chr16-779027;