Genetic Variant NM_032304.4:c.190C>G (chr16-728135-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032304.4(HAGHL):c.190C>G(p.Pro64Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 1,323,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

HAGHL
NM_032304.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.809

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050058186).

BP6

Variant 16-728135-C-G is Benign according to our data. Variant chr16-728135-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2610564.Status of the report is criteria_provided_single_submitter, 1 stars.

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.190C>G	p.Pro64Ala	missense	Exon 3 of 8	NP_115680.1	Q6PII5-2
HAGHL	NM_001323636.2		c.190C>G	p.Pro64Ala	missense	Exon 4 of 8	NP_001310565.1
HAGHL	NM_207112.2		c.190C>G	p.Pro64Ala	missense	Exon 4 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.190C>G	p.Pro64Ala	missense	Exon 3 of 8	ENSP00000374353.3	Q6PII5-2
HAGHL	ENST00000389701.9	TSL:1	n.295C>G		non_coding_transcript_exon	Exon 3 of 7
HAGHL	ENST00000341413.8	TSL:2	c.190C>G	p.Pro64Ala	missense	Exon 4 of 7	ENSP00000341952.4	Q6PII5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000144

AC:

AN:

69632

AF XY:

0.0000253

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:

0.00000378

AC:

AN:

1323628

Hom.:

Cov.:

AF XY:

0.00000768

AC XY:

AN XY:

651420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26044

American (AMR)

AF:

0.00

AC:

AN:

24040

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21906

East Asian (EAS)

AF:

0.00

AC:

AN:

29596

South Asian (SAS)

AF:

0.0000720

AC:

AN:

69398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3830

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051780

Other (OTH)

AF:

0.00

AC:

AN:

54692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Benign

9.1

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.17

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.68

M_CAP

Benign

0.023

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.91

PhyloP100

0.81

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.030

REVEL

Benign

0.19

Sift

Benign

0.60

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.058

MutPred

0.49

Gain of methylation at R68 (P = 0.0694)

MVP

0.26

MPC

0.19

ClinPred

0.018

GERP RS

0.57

PromoterAI

-0.071

Neutral

(source)

Varity_R

0.033

gMVP

0.15

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

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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