rs3800131

chr6-1918028-A-Cchr6-1918028-A-Gchr6-1918028-A-T

Variant summary

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

The NM_001500.4(GMDS):c.771+12075T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,126 control chromosomes in the GnomAD database, including 29,544 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 0.62 (29544 hom., cov: 33)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GMDS	NM_001500.4	c.771+12075T>G		intron_variant		ENST00000380815.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GMDS	ENST00000380815.5	c.771+12075T>G		intron_variant		1	NM_001500.4	P1
GMDS	ENST00000530927.5	c.681+12075T>G		intron_variant		1
GMDS	ENST00000380805.6	n.897+12075T>G		intron_variant, non_coding_transcript_variant		2
GMDS	ENST00000531690.5	n.250+12075T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94208 AN: 152008 Hom.: 29507 Cov.: 33

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.719

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.620 AC: 94301 AN: 152126 Hom.: 29544 Cov.: 33 AF XY: 0.625 AC XY: 46467 AN XY: 74334

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.661

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.608

Alfa AF: 0.638 Hom.: 31140

Bravo AF: 0.611

Asia WGS AF: 0.748 AC: 2602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.9
Dann	Benign	0.75

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: rs3800131; hg19: chr6-1918262;