rs9378688

chr6-2235399-G-Achr6-2235399-G-T

Variant summary

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

The NM_001500.4(GMDS):c.102+9922C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,150 control chromosomes in the GnomAD database, including 940 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 0.10 (940 hom., cov: 32)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMDS	NM_001500.4	c.102+9922C>T		intron_variant		ENST00000380815.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMDS	ENST00000380815.5	c.102+9922C>T		intron_variant		1	NM_001500.4	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15376 AN: 152032 Hom.: 942 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0977

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.101 AC: 15368 AN: 152150 Hom.: 940 Cov.: 32 AF XY: 0.105 AC XY: 7793 AN XY: 74364

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.120

Alfa AF: 0.120 Hom.: 1727

Bravo AF: 0.0932

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9378688; hg19: chr6-2235633;