Genetic Variant HAGH:p.Arg307Leu (chr16-1809290-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005326.6(HAGH):c.920G>T(p.Arg307Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R307Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HAGH
NM_005326.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

Publications

1 publications found

Variant links:

Genes affected

HAGH (HGNC:4805): (hydroxyacylglutathione hydrolase) The enzyme encoded by this gene is classified as a thiolesterase and is responsible for the hydrolysis of S-lactoyl-glutathione to reduced glutathione and D-lactate. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

HAGH links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2985716).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005326.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAGH	NM_005326.6	MANE Select	c.920G>T	p.Arg307Leu	missense	Exon 9 of 9	NP_005317.2	Q16775-1
HAGH	NM_001040427.2		c.776G>T	p.Arg259Leu	missense	Exon 10 of 10	NP_001035517.1	Q16775-2
HAGH	NM_001363912.1		c.*63G>T		3_prime_UTR	Exon 9 of 9	NP_001350841.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HAGH	ENST00000397356.8	TSL:1 MANE Select	c.920G>T	p.Arg307Leu	missense	Exon 9 of 9	ENSP00000380514.3	Q16775-1
HAGH	ENST00000945501.1		c.959G>T	p.Arg320Leu	missense	Exon 9 of 9	ENSP00000615560.1
HAGH	ENST00000851988.1		c.920G>T	p.Arg307Leu	missense	Exon 9 of 10	ENSP00000522047.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455412

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723248

African (AFR)

AF:

0.00

AC:

AN:

33372

American (AMR)

AF:

0.00

AC:

AN:

44414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25960

East Asian (EAS)

AF:

0.00

AC:

AN:

39508

South Asian (SAS)

AF:

0.00

AC:

AN:

85852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107204

Other (OTH)

AF:

0.00

AC:

AN:

60094

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.2

PhyloP100

1.4

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

REVEL

Uncertain

0.45

Sift

Uncertain

0.018

Sift4G

Uncertain

0.010

Polyphen

0.56

Vest4

0.23

MutPred

0.32

Loss of solvent accessibility (P = 0.089)

MVP

0.70

MPC

0.056

ClinPred

0.66

GERP RS

-0.12

Varity_R

0.24

gMVP

0.53

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