NM_138801.3:c.113G>A

Variant names:

• chr2-38666274-G-A
• NM_138801.3:c.113G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_138801.3(GALM):​c.113G>A​(p.Cys38Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALM NM_138801.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89
• Publications: 0 publications found

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, ClinGen, Labcorp Genetics (formerly Invitae)

GALM-AS1 (HGNC:41037):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.975

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.113G>A	p.Cys38Tyr	missense	Exon 1 of 7	NP_620156.1	A0A384MDW6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALM	ENST00000272252.10	TSL:1 MANE Select	c.113G>A	p.Cys38Tyr	missense	Exon 1 of 7	ENSP00000272252.5	Q96C23
	GALM	ENST00000862593.1		c.113G>A	p.Cys38Tyr	missense	Exon 1 of 8	ENSP00000532652.1
	GALM	ENST00000862591.1		c.113G>A	p.Cys38Tyr	missense	Exon 1 of 7	ENSP00000532650.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.9
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.93		Gain of sheet (P = 0.1539)
MVP		0.72
MPC		0.42
ClinPred		0.99	D
GERP RS		5.1
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.93
Mutation Taster		=62/38	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

hg19: chr2-38893416;