2-38675784-T-C

Position:

• chr2-38675784-T-C

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.191-128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 801,516 control chromosomes in the GnomAD database, including 3,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (896 hom., cov: 30)
  • Exomes 𝑓: 0.068 (3064 hom.)
• Consequence: GALM NM_138801.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

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=-0.93).
• BP6: Variant 2-38675784-T-C is Benign according to our data. Variant chr2-38675784-T-C is described in ClinVar as [Benign]. Clinvar id is 1179258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALM	NM_138801.3	c.191-128T>C		intron_variant		ENST00000272252.10	NP_620156.1
GALM	XM_011532540.3	c.191-128T>C		intron_variant			XP_011530842.1
GALM	XM_047443419.1	c.191-128T>C		intron_variant			XP_047299375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALM	ENST00000272252.10	c.191-128T>C		intron_variant		1	NM_138801.3	ENSP00000272252.5
GALM	ENST00000410063.5	c.190+9433T>C		intron_variant		3		ENSP00000386233.1
GALM	ENST00000427858.4	n.272-128T>C		intron_variant		4
GALM	ENST00000444351.5	n.110-128T>C		intron_variant		5		ENSP00000409083.1

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12931 AN: 151810 Hom.: 899 Cov.: 30

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0444

Gnomad OTH AF: 0.0817

GnomAD4 exome AF: 0.0685 AC: 44474 AN: 649588 Hom.: 3064 AF XY: 0.0698 AC XY: 23895 AN XY: 342510

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0637

Gnomad4 ASJ exome AF: 0.0509

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0238

Gnomad4 NFE exome AF: 0.0436

Gnomad4 OTH exome AF: 0.0715

GnomAD4 genome AF: 0.0852 AC: 12941 AN: 151928 Hom.: 896 Cov.: 30 AF XY: 0.0860 AC XY: 6387 AN XY: 74278

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0732

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0828

Alfa AF: 0.0625 Hom.: 60

Bravo AF: 0.0910

Asia WGS AF: 0.176 AC: 610 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 12, 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	-0.93
CADD	Benign	5.3
DANN	Benign	0.59

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: rs12052751; hg19: chr2-38902926; COSMIC: COSV55372362; COSMIC: COSV55372362;