rs13010022

Variant names:

• chr2-38682564-G-T
• rs13010022
• NM_138801.3:c.552+1078G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138801.3(GALM):​c.552+1078G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,094 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (886 hom., cov: 32)
• Consequence: GALM NM_138801.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795
• Publications: 1 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: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALM	NM_138801.3	c.552+1078G>T		intron_variant	Intron 3 of 6	ENST00000272252.10	NP_620156.1
GALM	XM_011532540.3	c.552+1078G>T		intron_variant	Intron 3 of 5		XP_011530842.1
GALM	XM_047443419.1	c.552+1078G>T		intron_variant	Intron 3 of 5		XP_047299375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALM	ENST00000272252.10	c.552+1078G>T		intron_variant	Intron 3 of 6	1	NM_138801.3	ENSP00000272252.5
GALM	ENST00000434934.1	c.192+1078G>T		intron_variant	Intron 1 of 4	3		ENSP00000399473.1
GALM	ENST00000410063.5	c.190+16213G>T		intron_variant	Intron 1 of 3	3		ENSP00000386233.1
GALM	ENST00000444351.5	n.471+1078G>T		intron_variant	Intron 3 of 6	5		ENSP00000409083.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15346 AN: 151976 Hom.: 880 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0905

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.101 AC: 15378 AN: 152094 Hom.: 886 Cov.: 32 AF XY: 0.105 AC XY: 7775 AN XY: 74344

African (AFR) AF: 0.121 AC: 5022 AN: 41464

American (AMR) AF: 0.103 AC: 1574 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3472

East Asian (EAS) AF: 0.201 AC: 1038 AN: 5162

South Asian (SAS) AF: 0.221 AC: 1062 AN: 4814

European-Finnish (FIN) AF: 0.0541 AC: 573 AN: 10598

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0791 AC: 5377 AN: 68002

Other (OTH) AF: 0.0896 AC: 189 AN: 2110

Alfa AF: 0.0888 Hom.: 104

Bravo AF: 0.103

Asia WGS AF: 0.212 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.42
DANN	Benign	0.62
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs13010022; hg19: chr2-38909706;