chr2-38666518-A-G

Variant names:

• chr2-38666518-A-G
• rs3821023
• NM_138801.3:c.190+167A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138801.3(GALM):​c.190+167A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,018 control chromosomes in the GnomAD database, including 6,756 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (6756 hom., cov: 32)
• Consequence: GALM NM_138801.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02
• Publications: 20 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)

ENSG00000232518 (HGNC:41037):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-38666518-A-G is Benign according to our data. Variant chr2-38666518-A-G is described in ClinVar as Benign. ClinVar VariationId is 1274627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138801.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALM	NM_138801.3	MANE Select	c.190+167A>G		intron	N/A	NP_620156.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALM	ENST00000272252.10	TSL:1 MANE Select	c.190+167A>G		intron	N/A	ENSP00000272252.5
	GALM	ENST00000410063.5	TSL:3	c.190+167A>G		intron	N/A	ENSP00000386233.1
	GALM	ENST00000427858.4	TSL:4	n.271+167A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36946 AN: 151900 Hom.: 6742 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.0897

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.243 AC: 37004 AN: 152018 Hom.: 6756 Cov.: 32 AF XY: 0.243 AC XY: 18046 AN XY: 74354

African (AFR) AF: 0.509 AC: 21061 AN: 41338

American (AMR) AF: 0.175 AC: 2685 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3464

East Asian (EAS) AF: 0.389 AC: 2009 AN: 5158

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4826

European-Finnish (FIN) AF: 0.0897 AC: 953 AN: 10622

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8069 AN: 67992

Other (OTH) AF: 0.205 AC: 432 AN: 2112

Alfa AF: 0.160 Hom.: 12903

Bravo AF: 0.262

Asia WGS AF: 0.323 AC: 1123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.20
DANN	Benign	0.33
PhyloP100		-1.0
PromoterAI		0.14	Neutral
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: rs3821023; hg19: chr2-38893660;