rs6741892

Positions:

chr2-38689828-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1760 hom., cov: 32)

Exomes 𝑓: 0.094 ( 8198 hom. )

Consequence

GALM
NM_138801.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.23

Variant links:

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 links:

LOC124905993 (HGNC:):

LOC124905993 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GALM	NM_138801.3 linkuse as main transcript	c.568A>T	p.Asn190Tyr	missense_variant	4/7	ENST00000272252.10
LOC124905993	XR_007086292.1 linkuse as main transcript	n.220-4154T>A		intron_variant, non_coding_transcript_variant
GALM	XM_011532540.3 linkuse as main transcript	c.568A>T	p.Asn190Tyr	missense_variant	4/6
GALM	XM_047443419.1 linkuse as main transcript	c.568A>T	p.Asn190Tyr	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GALM	ENST00000272252.10 linkuse as main transcript	c.568A>T	p.Asn190Tyr	missense_variant	4/7	1	NM_138801.3	P1
GALM	ENST00000434934.1 linkuse as main transcript	c.208A>T	p.Asn70Tyr	missense_variant	2/5	3
GALM	ENST00000410063.5 linkuse as main transcript	c.190+23477A>T		intron_variant		3
GALM	ENST00000444351.5 linkuse as main transcript	c.487A>T	p.Asn163Tyr	missense_variant, NMD_transcript_variant	4/7	5

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20280

AN:

152070

Hom.:

1746

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.123

AC:

30385

AN:

246072

Hom.:

2387

AF XY:

0.123

AC XY:

16404

AN XY:

133262

show subpopulations

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 SAS exome

AF:

0.222

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.:

AF XY:

0.0973

AC XY:

70248

AN XY:

721822

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.213

Gnomad4 FIN exome

AF:

0.0587

Gnomad4 NFE exome

AF:

0.0761

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.134

AC:

20330

AN:

152188

Hom.:

1760

Cov.:

AF XY:

0.136

AC XY:

10094

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.223

Gnomad4 FIN

AF:

0.0542

Gnomad4 NFE

AF:

0.0807

Gnomad4 OTH

AF:

0.115

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

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Galactosemia 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

GALM-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.64

PROVEAN

Benign

4.8

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

0.85

T;T

Polyphen

0.0

B;.

Vest4

0.11

MPC

0.059

ClinPred

0.0035

GERP RS

4.8

Varity_R

0.26

gMVP

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over