16-728534-C-T

Variant names:

• chr16-728534-C-T
• rs374833821
• NM_032304.4:c.428C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032304.4(HAGHL):​c.428C>T​(p.Ser143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000291 in 1,376,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0000029 (0 hom.)
• Consequence: HAGHL NM_032304.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02709043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAGHL	NM_032304.4	c.428C>T	p.Ser143Leu	missense_variant	Exon 5 of 8	ENST00000389703.8	NP_115680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HAGHL	ENST00000389703.8	c.428C>T	p.Ser143Leu	missense_variant	Exon 5 of 8	1	NM_032304.4	ENSP00000374353.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000161 AC: 2 AN: 124248 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 68182

Gnomad AFR exome AF: 0.000165

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000466

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000291 AC: 4 AN: 1376760 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 679204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000563

Gnomad4 SAS exome AF: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.29e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ESP6500AA AF: 0.000347 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000132 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.34	T;.;T;.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.73	T;T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.027	T;T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.39	N;.;.;N;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N;N;N;N;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0090	D;D;D;D;.
Sift4G	Benign	0.083	T;D;D;D;D
Polyphen		0.022	B;.;B;B;.
Vest4		0.12
MVP		0.31
MPC		0.17
ClinPred		0.031	T
GERP RS		-8.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.049
gMVP		0.30

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: rs374833821; hg19: chr16-778534;