2-38666274-G-A

Position:

• chr2-38666274-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 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

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 Likely_pathogenic. Variant got 6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALM	NM_138801.3	c.113G>A	p.Cys38Tyr	missense_variant	1/7	ENST00000272252.10	NP_620156.1
GALM	XM_011532540.3	c.113G>A	p.Cys38Tyr	missense_variant	1/6		XP_011530842.1
GALM	XM_047443419.1	c.113G>A	p.Cys38Tyr	missense_variant	1/6		XP_047299375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALM	ENST00000272252.10	c.113G>A	p.Cys38Tyr	missense_variant	1/7	1	NM_138801.3	ENSP00000272252.5
GALM	ENST00000410063.5	c.113G>A	p.Cys38Tyr	missense_variant	1/4	3		ENSP00000386233.1
GALM	ENST00000427858.4	n.194G>A		non_coding_transcript_exon_variant	1/4	4
GALM	ENST00000444351.5	n.32G>A		non_coding_transcript_exon_variant	1/7	5		ENSP00000409083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.113G>A (p.C38Y) alteration is located in exon 1 (coding exon 1) of the GALM gene. This alteration results from a G to A substitution at nucleotide position 113, causing the cysteine (C) at amino acid position 38 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Pathogenic	2.9	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.8	D;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.87
MutPred		0.93		Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);
MVP		0.72
MPC		0.42
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.97
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-38893416;