NM_138801.3:c.13A>C

Variant names:

• chr2-38666174-A-C
• rs753623665
• NM_138801.3:c.13A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138801.3(GALM):​c.13A>C​(p.Thr5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,424 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. T5A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: GALM NM_138801.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

GALM-AS1 (HGNC:41037):

ACMG classification

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=0.15310833).

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.13A>C	p.Thr5Pro	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.13A>C	p.Thr5Pro	missense	Exon 1 of 7	ENSP00000272252.5	Q96C23
	GALM	ENST00000862593.1		c.13A>C	p.Thr5Pro	missense	Exon 1 of 8	ENSP00000532652.1
	GALM	ENST00000862591.1		c.13A>C	p.Thr5Pro	missense	Exon 1 of 7	ENSP00000532650.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460236 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726440

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111150

Other (OTH) AF: 0.0000332 AC: 2 AN: 60318

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.18
Sift	Benign	0.064	T
Sift4G	Benign	0.070	T
Polyphen		0.22	B
Vest4		0.22
MutPred		0.37		Loss of sheet (P = 0.0104)
MVP		0.092
MPC		0.075
ClinPred		0.64	D
GERP RS		3.9
PromoterAI		-0.11	Neutral
Varity_R		0.51
gMVP		0.67
Mutation Taster		=56/44	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

dbSNP: rs753623665; hg19: chr2-38893316;