2-38666283-C-T

Position:

• chr2-38666283-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138801.3(GALM):​c.122C>T​(p.Thr41Ile) 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. 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: 2.40

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32867098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALM	NM_138801.3	c.122C>T	p.Thr41Ile	missense_variant	1/7	ENST00000272252.10	NP_620156.1
GALM	XM_011532540.3	c.122C>T	p.Thr41Ile	missense_variant	1/6		XP_011530842.1
GALM	XM_047443419.1	c.122C>T	p.Thr41Ile	missense_variant	1/6		XP_047299375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALM	ENST00000272252.10	c.122C>T	p.Thr41Ile	missense_variant	1/7	1	NM_138801.3	ENSP00000272252.5
GALM	ENST00000410063.5	c.122C>T	p.Thr41Ile	missense_variant	1/4	3		ENSP00000386233.1
GALM	ENST00000427858.4	n.203C>T		non_coding_transcript_exon_variant	1/4	4
GALM	ENST00000444351.5	n.41C>T		non_coding_transcript_exon_variant	1/7	5		ENSP00000409083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 24, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GALM protein function. This variant has not been reported in the literature in individuals affected with GALM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 41 of the GALM protein (p.Thr41Ile). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.39	N
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.0	D;N
REVEL	Benign	0.18
Sift	Benign	0.054	T;D
Sift4G	Benign	0.21	T;D
Polyphen		0.90	P;.
Vest4		0.32
MutPred		0.60		Loss of disorder (P = 0.0738);Loss of disorder (P = 0.0738);
MVP		0.36
MPC		0.23
ClinPred		0.86	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.68
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs1263376779; hg19: chr2-38893425; COSMIC: COSV55372925; COSMIC: COSV55372925;