Genetic Variant GALM:c.345+1784A>G (chr2-38677850-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138801.3(GALM):c.345+1784A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 151,804 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.062 ( 399 hom., cov: 32)

Consequence

GALM
NM_138801.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.894

Publications

1 publications found

Variant links:

Genes affected

GALM (HGNC:24063): (galactose mutarotase) This gene encodes an enzyme that catalyzes the epimerization of hexose sugars such as glucose and galactose. The encoded protein is expressed in the cytoplasm and has a preference for galactose. The encoded protein may be required for normal galactose metabolism by maintaining the equilibrium of alpha and beta anomers of galactose.[provided by RefSeq, Mar 2009]

GALM Gene-Disease associations (from GenCC):

galactosemia 4
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

GALM links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_138801.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138801.3. 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
	GALM	NM_138801.3	MANE Select	c.345+1784A>G		intron	N/A	NP_620156.1	A0A384MDW6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GALM	ENST00000272252.10	TSL:1 MANE Select	c.345+1784A>G	intron	N/A	ENSP00000272252.5	Q96C23
GALM	ENST00000862593.1		c.345+1784A>G	intron	N/A	ENSP00000532652.1
GALM	ENST00000862591.1		c.345+1784A>G	intron	N/A	ENSP00000532650.1

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9368

AN:

151694

Hom.:

400

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0876

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.0672

Gnomad ASJ

AF:

0.0450

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.0865

Gnomad NFE

AF:

0.0416

Gnomad OTH

AF:

0.0648

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0618

AC:

9381

AN:

151804

Hom.:

399

Cov.:

AF XY:

0.0624

AC XY:

4632

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.0876

AC:

3620

AN:

41302

American (AMR)

AF:

0.0672

AC:

1026

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0450

AC:

156

AN:

3468

East Asian (EAS)

AF:

0.152

AC:

778

AN:

5116

South Asian (SAS)

AF:

0.102

AC:

487

AN:

4796

European-Finnish (FIN)

AF:

0.0184

AC:

195

AN:

10610

Middle Eastern (MID)

AF:

0.0966

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0416

AC:

2824

AN:

67934

Other (OTH)

AF:

0.0660

AC:

139

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

421

841

1262

1682

2103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0488

Hom.:

180

Bravo

AF:

0.0651

Asia WGS

AF:

0.0990

AC:

343

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.039

(source)

DANN

Benign

0.40

PhyloP100

-0.89

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over