2-38675812-G-T

Position:

• chr2-38675812-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_138801.3(GALM):​c.191-100G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,069,470 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (49 hom., cov: 30)
  • Exomes 𝑓: 0.0016 (28 hom.)
• Consequence: GALM NM_138801.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.882

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 2-38675812-G-T is Benign according to our data. Variant chr2-38675812-G-T is described in ClinVar as [Benign]. Clinvar id is 1295014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2048/151880) while in subpopulation AFR AF= 0.0468 (1937/41390). AF 95% confidence interval is 0.0451. There are 49 homozygotes in gnomad4. There are 986 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALM	NM_138801.3	c.191-100G>T		intron_variant		ENST00000272252.10	NP_620156.1
GALM	XM_011532540.3	c.191-100G>T		intron_variant			XP_011530842.1
GALM	XM_047443419.1	c.191-100G>T		intron_variant			XP_047299375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALM	ENST00000272252.10	c.191-100G>T		intron_variant		1	NM_138801.3	ENSP00000272252.5
GALM	ENST00000410063.5	c.190+9461G>T		intron_variant		3		ENSP00000386233.1
GALM	ENST00000427858.4	n.272-100G>T		intron_variant		4
GALM	ENST00000444351.5	n.110-100G>T		intron_variant		5		ENSP00000409083.1

Frequencies

GnomAD3 genomes AF: 0.0134 AC: 2041 AN: 151762 Hom.: 49 Cov.: 30

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00421

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00819

GnomAD4 exome AF: 0.00161 AC: 1478 AN: 917590 Hom.: 28 AF XY: 0.00134 AC XY: 634 AN XY: 472526

Gnomad4 AFR exome AF: 0.0467

Gnomad4 AMR exome AF: 0.00240

Gnomad4 ASJ exome AF: 0.00341

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000432

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000139

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.0135 AC: 2048 AN: 151880 Hom.: 49 Cov.: 30 AF XY: 0.0133 AC XY: 986 AN XY: 74260

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.00421

Gnomad4 ASJ AF: 0.00347

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00810

Alfa AF: 0.000775 Hom.: 0

Bravo AF: 0.0154

Asia WGS AF: 0.00144 AC: 5 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 25, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.53

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: rs149949698; hg19: chr2-38902954;