Variant 2-38666174-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138801.3(GALM):c.13A>T(p.Thr5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GALM
NM_138801.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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 links:

GALM (HGNC:):

GALM links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.083355576).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALM	NM_138801.3 linkuse as main transcript	c.13A>T	p.Thr5Ser	missense_variant	1/7	ENST00000272252.10	NP_620156.1	Q96C23A0A384MDW6
GALM	XM_011532540.3 linkuse as main transcript	c.13A>T	p.Thr5Ser	missense_variant	1/6		XP_011530842.1	Q96C23
GALM	XM_047443419.1 linkuse as main transcript	c.13A>T	p.Thr5Ser	missense_variant	1/6		XP_047299375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GALM	ENST00000272252.10 linkuse as main transcript	c.13A>T	p.Thr5Ser	missense_variant	1/7	1	NM_138801.3	ENSP00000272252.5	Q96C23
GALM	ENST00000410063.5 linkuse as main transcript	c.13A>T	p.Thr5Ser	missense_variant	1/4	3		ENSP00000386233.1	B8ZZ75
GALM	ENST00000427858.4 linkuse as main transcript	n.94A>T		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248558

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726440

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 17, 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with GALM-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 5 of the GALM protein (p.Thr5Ser). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.083

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.89

L;.

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.082

Sift

Benign

0.39

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0010

B;.

Vest4

0.079

MutPred

0.21

Gain of disorder (P = 0.0279);Gain of disorder (P = 0.0279);

MVP

0.048

MPC

0.047

ClinPred

0.029

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.063

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over