NM_138801.3:c.191-100G>T

Variant names:

• chr2-38675812-G-T
• rs149949698
• NM_138801.3:c.191-100G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

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.191-100G>T		intron	N/A	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.191-100G>T		intron	N/A	ENSP00000272252.5	Q96C23
	GALM	ENST00000862593.1		c.191-100G>T		intron	N/A	ENSP00000532652.1
	GALM	ENST00000862591.1		c.191-100G>T		intron	N/A	ENSP00000532650.1

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

African (AFR) AF: 0.0467 AC: 1070 AN: 22908

American (AMR) AF: 0.00240 AC: 98 AN: 40752

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 68 AN: 19916

East Asian (EAS) AF: 0.00 AC: 0 AN: 35976

South Asian (SAS) AF: 0.0000432 AC: 3 AN: 69438

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48240

Middle Eastern (MID) AF: 0.00114 AC: 4 AN: 3516

European-Non Finnish (NFE) AF: 0.000139 AC: 88 AN: 635236

Other (OTH) AF: 0.00353 AC: 147 AN: 41608

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

African (AFR) AF: 0.0468 AC: 1937 AN: 41390

American (AMR) AF: 0.00421 AC: 64 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00347 AC: 12 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67958

Other (OTH) AF: 0.00810 AC: 17 AN: 2098

Alfa AF: 0.00221 Hom.: 0

Bravo AF: 0.0154

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.37
DANN	Benign	0.53
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism

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: rs149949698; hg19: chr2-38902954;