NM_001500.4:c.102+9922C>T

Variant names:

• chr6-2235399-G-A
• rs9378688
• NM_001500.4:c.102+9922C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.9).
• 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 rank	MANE	Protein	UniProt
GMDS	NM_001500.4	c.102+9922C>T		intron_variant	Intron 1 of 10	ENST00000380815.5	NP_001491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMDS	ENST00000380815.5	c.102+9922C>T		intron_variant	Intron 1 of 10	1	NM_001500.4	ENSP00000370194.4

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

African (AFR) AF: 0.0438 AC: 1817 AN: 41516

American (AMR) AF: 0.0976 AC: 1494 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3472

East Asian (EAS) AF: 0.178 AC: 919 AN: 5166

South Asian (SAS) AF: 0.171 AC: 825 AN: 4814

European-Finnish (FIN) AF: 0.146 AC: 1541 AN: 10562

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7777 AN: 68002

Other (OTH) AF: 0.120 AC: 252 AN: 2108

Alfa AF: 0.114 Hom.: 2556

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
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9378688; hg19: chr6-2235633;