2-38675880-T-A

Position:

• chr2-38675880-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138801.3(GALM):​c.191-32T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 1,611,636 control chromosomes in the GnomAD database, including 7,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (586 hom., cov: 31)
  • Exomes 𝑓: 0.089 (7145 hom.)
• Consequence: GALM NM_138801.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.636

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-38675880-T-A is Benign according to our data. Variant chr2-38675880-T-A is described in ClinVar as [Benign]. Clinvar id is 1268639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALM	NM_138801.3	c.191-32T>A		intron_variant		ENST00000272252.10	NP_620156.1
GALM	XM_011532540.3	c.191-32T>A		intron_variant			XP_011530842.1
GALM	XM_047443419.1	c.191-32T>A		intron_variant			XP_047299375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALM	ENST00000272252.10	c.191-32T>A		intron_variant		1	NM_138801.3	ENSP00000272252.5
GALM	ENST00000410063.5	c.190+9529T>A		intron_variant		3		ENSP00000386233.1
GALM	ENST00000427858.4	n.272-32T>A		intron_variant		4
GALM	ENST00000444351.5	n.110-32T>A		intron_variant		5		ENSP00000409083.1

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11157 AN: 151730 Hom.: 581 Cov.: 31

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0789

Gnomad OTH AF: 0.0781

GnomAD3 exomes AF: 0.108 AC: 27162 AN: 251112 Hom.: 2010 AF XY: 0.112 AC XY: 15193 AN XY: 135712

Gnomad AFR exome AF: 0.0212

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.232

Gnomad SAS exome AF: 0.217

Gnomad FIN exome AF: 0.0592

Gnomad NFE exome AF: 0.0777

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.0885 AC: 129203 AN: 1459788 Hom.: 7145 Cov.: 30 AF XY: 0.0922 AC XY: 66971 AN XY: 726258

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.0590

Gnomad4 NFE exome AF: 0.0757

Gnomad4 OTH exome AF: 0.0978

GnomAD4 genome AF: 0.0736 AC: 11176 AN: 151848 Hom.: 586 Cov.: 31 AF XY: 0.0779 AC XY: 5783 AN XY: 74218

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.0925

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.0544

Gnomad4 NFE AF: 0.0788

Gnomad4 OTH AF: 0.0773

Alfa AF: 0.0775 Hom.: 104

Bravo AF: 0.0715

Asia WGS AF: 0.213 AC: 738 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.3
DANN	Benign	0.89

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: rs17576472; hg19: chr2-38903022; COSMIC: COSV55370820; COSMIC: COSV55370820;