rs234937

chr6-2230018-T-Cchr6-2230018-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001500.4(GMDS):c.102+15303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 142,010 control chromosomes in the GnomAD database, including 10,407 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 0.36 (10407 hom., cov: 29)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

Genes affected

GMDS (HGNC:4369): (GDP-mannose 4,6-dehydratase) GDP-mannose 4,6-dehydratase (GMD; EC 4.2.1.47) catalyzes the conversion of GDP-mannose to GDP-4-keto-6-deoxymannose, the first step in the synthesis of GDP-fucose from GDP-mannose, using NADP+ as a cofactor. The second and third steps of the pathway are catalyzed by a single enzyme, GDP-keto-6-deoxymannose 3,5-epimerase, 4-reductase, designated FX in humans (MIM 137020).[supplied by OMIM, Aug 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMDS	NM_001500.4	c.102+15303A>G		intron_variant		ENST00000380815.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMDS	ENST00000380815.5	c.102+15303A>G		intron_variant		1	NM_001500.4	P1
	ENST00000650019.1	n.565T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 50646 AN: 141914 Hom.: 10394 Cov.: 29

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.520

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.357 AC: 50705 AN: 142010 Hom.: 10407 Cov.: 29 AF XY: 0.355 AC XY: 24625 AN XY: 69430

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.382

Alfa AF: 0.269 Hom.: 5442

Bravo AF: 0.417

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.0
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs234937; hg19: chr6-2230252;