rs755242305

Variant names:

• chr16-727567-G-A
• rs755242305
• NM_032304.4:c.58G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-727567-G-A
• chr16-727567-G-T

Variant summary

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

The NM_032304.4(HAGHL):​c.58G>A​(p.Glu20Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,611,898 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: HAGHL NM_032304.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• Publications: 2 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: 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_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.58G>A	p.Glu20Lys	missense	Exon 1 of 8	NP_115680.1	Q6PII5-2
	HAGHL	NM_001323636.2		c.58G>A	p.Glu20Lys	missense	Exon 2 of 8	NP_001310565.1
	HAGHL	NM_207112.2		c.58G>A	p.Glu20Lys	missense	Exon 2 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.58G>A	p.Glu20Lys	missense	Exon 1 of 8	ENSP00000374353.3	Q6PII5-2
	HAGHL	ENST00000389701.9	TSL:1	n.163G>A		non_coding_transcript_exon	Exon 1 of 7
	HAGHL	ENST00000341413.8	TSL:2	c.58G>A	p.Glu20Lys	missense	Exon 2 of 7	ENSP00000341952.4	Q6PII5-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152206 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000816 AC: 2 AN: 245142 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000917

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000349 AC: 51 AN: 1459692 Hom.: 0 Cov.: 30 AF XY: 0.0000386 AC XY: 28 AN XY: 726162

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152206 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74354

African (AFR) AF: 0.0000241 AC: 1 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000830 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Benign	1.1	L
PhyloP100		1.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.61
Sift	Benign	0.090	T
Sift4G	Benign	0.088	T
Polyphen		0.57	P
Vest4		0.35
MutPred		0.48		Gain of methylation at E20 (P = 0.0196)
MVP		0.50
MPC		0.27
ClinPred		0.60	D
GERP RS		2.5
PromoterAI		0.012	Neutral
Varity_R		0.13
gMVP		0.45
Mutation Taster		=83/17	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: rs755242305; hg19: chr16-777567;