Genetic Variant NM_032304.4:c.574G>T (chr16-728869-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032304.4(HAGHL):c.574G>T(p.Val192Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,156 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V192M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HAGHL
NM_032304.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

1 publications found

Variant links:

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]

HAGHL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2279819).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAGHL	NM_032304.4	MANE Select	c.574G>T	p.Val192Leu	missense	Exon 6 of 8	NP_115680.1	Q6PII5-2
HAGHL	NM_001323636.2		c.574G>T	p.Val192Leu	missense	Exon 7 of 8	NP_001310565.1
HAGHL	NM_207112.2		c.574G>T	p.Val192Leu	missense	Exon 7 of 7	NP_996995.1	Q6PII5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAGHL	ENST00000389703.8	TSL:1 MANE Select	c.574G>T	p.Val192Leu	missense	Exon 6 of 8	ENSP00000374353.3	Q6PII5-2
HAGHL	ENST00000389701.9	TSL:1	n.761G>T		non_coding_transcript_exon	Exon 5 of 7
HAGHL	ENST00000341413.8	TSL:2	c.574G>T	p.Val192Leu	missense	Exon 7 of 7	ENSP00000341952.4	Q6PII5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000825

AC:

AN:

242414

AF XY:

0.00000756

show subpopulations

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457156

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51694

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110374

Other (OTH)

AF:

0.00

AC:

AN:

60230

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.047

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.23

MetaSVM

Uncertain

0.52

MutationAssessor

Benign

0.045

PhyloP100

1.4

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.41

Sift

Benign

0.63

Sift4G

Benign

0.47

Polyphen

0.99

Vest4

0.39

MutPred

0.49

Loss of MoRF binding (P = 0.103)

MVP

0.51

MPC

0.25

ClinPred

0.43

GERP RS

4.7

Varity_R

0.16

gMVP

0.40

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over