rs10495881

Variant names:

• chr2-38677850-A-G
• rs10495881
• NM_138801.3:c.345+1784A>G

Variant summary

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

The NM_138801.3(GALM):​c.345+1784A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 151,804 control chromosomes in the GnomAD database, including 399 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 0.062 (399 hom., cov: 32)
• Consequence: GALM NM_138801.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALM	NM_138801.3	c.345+1784A>G		intron_variant	Intron 2 of 6	ENST00000272252.10	NP_620156.1
GALM	XM_011532540.3	c.345+1784A>G		intron_variant	Intron 2 of 5		XP_011530842.1
GALM	XM_047443419.1	c.345+1784A>G		intron_variant	Intron 2 of 5		XP_047299375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALM	ENST00000272252.10	c.345+1784A>G		intron_variant	Intron 2 of 6	1	NM_138801.3	ENSP00000272252.5
GALM	ENST00000410063.5	c.190+11499A>G		intron_variant	Intron 1 of 3	3		ENSP00000386233.1
GALM	ENST00000427858.4	n.426+1784A>G		intron_variant	Intron 2 of 3	4
GALM	ENST00000444351.5	n.264+1784A>G		intron_variant	Intron 2 of 6	5		ENSP00000409083.1

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9368 AN: 151694 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0865

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0648

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

GnomAD4 genome AF: 0.0618 AC: 9381 AN: 151804 Hom.: 399 Cov.: 32 AF XY: 0.0624 AC XY: 4632 AN XY: 74192

African (AFR) AF: 0.0876 AC: 3620 AN: 41302

American (AMR) AF: 0.0672 AC: 1026 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0450 AC: 156 AN: 3468

East Asian (EAS) AF: 0.152 AC: 778 AN: 5116

South Asian (SAS) AF: 0.102 AC: 487 AN: 4796

European-Finnish (FIN) AF: 0.0184 AC: 195 AN: 10610

Middle Eastern (MID) AF: 0.0966 AC: 28 AN: 290

European-Non Finnish (NFE) AF: 0.0416 AC: 2824 AN: 67934

Other (OTH) AF: 0.0660 AC: 139 AN: 2106

Alfa AF: 0.0488 Hom.: 180

Bravo AF: 0.0651

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.039
DANN	Benign	0.40
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10495881; hg19: chr2-38904992;