chr2-38689828-A-T

Variant names:

• chr2-38689828-A-T
• rs6741892
• NM_138801.3:c.568A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_138801.3(GALM):​c.568A>T​(p.Asn190Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0981 in 1,601,982 control chromosomes in the GnomAD database, including 9,958 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1760 hom., cov: 32)
  • Exomes 𝑓: 0.094 (8198 hom.)
• Consequence: GALM NM_138801.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 5.23
• Publications: 32 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)

LOC124905993 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011598766).
• BP6: Variant 2-38689828-A-T is Benign according to our data. Variant chr2-38689828-A-T is described in ClinVar as Benign. ClinVar VariationId is 1222775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALM	NM_138801.3	MANE Select	c.568A>T	p.Asn190Tyr	missense	Exon 4 of 7	NP_620156.1	A0A384MDW6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALM	ENST00000272252.10	TSL:1 MANE Select	c.568A>T	p.Asn190Tyr	missense	Exon 4 of 7	ENSP00000272252.5	Q96C23
	GALM	ENST00000862593.1		c.568A>T	p.Asn190Tyr	missense	Exon 4 of 8	ENSP00000532652.1
	GALM	ENST00000862591.1		c.568A>T	p.Asn190Tyr	missense	Exon 4 of 7	ENSP00000532650.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20280 AN: 152070 Hom.: 1746 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.123 AC: 30385 AN: 246072 AF XY: 0.123

Gnomad AFR exome AF: 0.242

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.205

Gnomad FIN exome AF: 0.0586

Gnomad NFE exome AF: 0.0798

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0944 AC: 136875 AN: 1449794 Hom.: 8198 Cov.: 28 AF XY: 0.0973 AC XY: 70248 AN XY: 721822

African (AFR) AF: 0.242 AC: 8014 AN: 33062

American (AMR) AF: 0.124 AC: 5448 AN: 43842

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2943 AN: 26024

East Asian (EAS) AF: 0.202 AC: 7975 AN: 39502

South Asian (SAS) AF: 0.213 AC: 18070 AN: 85006

European-Finnish (FIN) AF: 0.0587 AC: 3130 AN: 53360

Middle Eastern (MID) AF: 0.126 AC: 724 AN: 5750

European-Non Finnish (NFE) AF: 0.0761 AC: 83927 AN: 1103348

Other (OTH) AF: 0.111 AC: 6644 AN: 59900

GnomAD4 genome AF: 0.134 AC: 20330 AN: 152188 Hom.: 1760 Cov.: 32 AF XY: 0.136 AC XY: 10094 AN XY: 74412

African (AFR) AF: 0.233 AC: 9673 AN: 41496

American (AMR) AF: 0.112 AC: 1706 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3468

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5172

South Asian (SAS) AF: 0.223 AC: 1075 AN: 4828

European-Finnish (FIN) AF: 0.0542 AC: 575 AN: 10602

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0807 AC: 5489 AN: 68016

Other (OTH) AF: 0.115 AC: 243 AN: 2112

Alfa AF: 0.0929 Hom.: 566

Bravo AF: 0.140

TwinsUK AF: 0.0755 AC: 280

ALSPAC AF: 0.0810 AC: 312

ESP6500AA AF: 0.233 AC: 1027

ESP6500EA AF: 0.0794 AC: 683

ExAC AF: 0.127 AC: 15463

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Galactosemia 4 (1)
-	-	1	GALM-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.79
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		5.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	4.8	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	0.85	T
Polyphen		0.0	B
Vest4		0.11
MPC		0.059
ClinPred		0.0035	T
GERP RS		4.8
Varity_R		0.26
gMVP		0.65
Mutation Taster		=96/4	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: rs6741892; hg19: chr2-38916970; COSMIC: COSV55370832;