6-1707020-C-T

Variant names:

• chr6-1707020-C-T
• rs9503012
• NM_001500.4:c.987+19396G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001500.4(GMDS):​c.987+19396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,098 control chromosomes in the GnomAD database, including 33,083 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 0.64 (33083 hom., cov: 33)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.962
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMDS	NM_001500.4	c.987+19396G>A		intron_variant	Intron 9 of 10	ENST00000380815.5	NP_001491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMDS	ENST00000380815.5	c.987+19396G>A		intron_variant	Intron 9 of 10	1	NM_001500.4	ENSP00000370194.4
GMDS	ENST00000530927.5	c.897+19396G>A		intron_variant	Intron 9 of 10	1		ENSP00000436726.1
GMDS	ENST00000380805.6	n.1249+10488G>A		intron_variant	Intron 4 of 5	2
GMDS	ENST00000533279.1	n.62+19396G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96799 AN: 151980 Hom.: 33080 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.901

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.637 AC: 96830 AN: 152098 Hom.: 33083 Cov.: 33 AF XY: 0.644 AC XY: 47849 AN XY: 74334

African (AFR) AF: 0.361 AC: 14974 AN: 41458

American (AMR) AF: 0.704 AC: 10762 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2504 AN: 3472

East Asian (EAS) AF: 0.901 AC: 4668 AN: 5182

South Asian (SAS) AF: 0.779 AC: 3748 AN: 4814

European-Finnish (FIN) AF: 0.783 AC: 8280 AN: 10578

Middle Eastern (MID) AF: 0.692 AC: 202 AN: 292

European-Non Finnish (NFE) AF: 0.729 AC: 49561 AN: 67996

Other (OTH) AF: 0.668 AC: 1409 AN: 2108

Alfa AF: 0.692 Hom.: 96341

Bravo AF: 0.619

Asia WGS AF: 0.777 AC: 2700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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: rs9503012; hg19: chr6-1707254;