2-38666166-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_ModerateBP6_Moderate

The NM_138801.3(GALM):​c.5C>T​(p.Ala2Val) 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 1,458,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GALM
NM_138801.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1
In a modified_residue N-acetylalanine (size 0) in uniprot entity GALM_HUMAN
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0727061).
BP6
Variant 2-38666166-C-T is Benign according to our data. Variant chr2-38666166-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3098041.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GALMNM_138801.3 linkc.5C>T p.Ala2Val missense_variant 1/7 ENST00000272252.10 NP_620156.1 Q96C23A0A384MDW6
GALMXM_011532540.3 linkc.5C>T p.Ala2Val missense_variant 1/6 XP_011530842.1 Q96C23
GALMXM_047443419.1 linkc.5C>T p.Ala2Val missense_variant 1/6 XP_047299375.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GALMENST00000272252.10 linkc.5C>T p.Ala2Val missense_variant 1/71 NM_138801.3 ENSP00000272252.5 Q96C23
GALMENST00000410063.5 linkc.5C>T p.Ala2Val missense_variant 1/43 ENSP00000386233.1 B8ZZ75
GALMENST00000427858.4 linkn.86C>T non_coding_transcript_exon_variant 1/44

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000405
AC:
1
AN:
247136
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133678
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000547
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:
2
AN:
1458428
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
725442
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000505
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.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJan 31, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
7.3
DANN
Benign
0.95
DEOGEN2
Benign
0.20
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.58
T;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.073
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.35
N;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.62
N;N
REVEL
Benign
0.024
Sift
Benign
0.63
T;T
Sift4G
Benign
0.26
T;T
Polyphen
0.0
B;.
Vest4
0.11
MutPred
0.28
Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP
0.16
MPC
0.051
ClinPred
0.044
T
GERP RS
1.7
Varity_R
0.076
gMVP
0.30

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.

Other links and lift over

dbSNP: rs1159501195; hg19: chr2-38893308; API