rs3046543

chr6-1949358-GTATA-Gchr6-1949358-GTATA-GTATATATA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001500.4(GMDS):c.643+10505_643+10508del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,874 control chromosomes in the GnomAD database, including 5,931 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5931 hom., cov: 25)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMDS	NM_001500.4	c.643+10505_643+10508del		intron_variant		ENST00000380815.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMDS	ENST00000380815.5	c.643+10505_643+10508del		intron_variant		1	NM_001500.4	P1
GMDS	ENST00000530927.5	c.553+10505_553+10508del		intron_variant		1
GMDS	ENST00000530459.1	n.396+10505_396+10508del		intron_variant, non_coding_transcript_variant		3
GMDS	ENST00000531690.5	n.122+10505_122+10508del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37153 AN: 151756 Hom.: 5894 Cov.: 25

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.245 AC: 37242 AN: 151874 Hom.: 5931 Cov.: 25 AF XY: 0.247 AC XY: 18325 AN XY: 74232

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.206

Alfa AF: 0.211 Hom.: 512

Bravo AF: 0.250

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3046543; hg19: chr6-1949592;