chr6-2229830-G-T

Variant names:

• chr6-2229830-G-T
• rs9405550
• NM_001500.4:c.102+15491C>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.102+15491C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,076 control chromosomes in the GnomAD database, including 1,022 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 0.11 (1022 hom., cov: 32)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 5 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]

ENSG00000285603 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001500.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMDS	NM_001500.4	MANE Select	c.102+15491C>A		intron	N/A	NP_001491.1	O60547-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMDS	ENST00000380815.5	TSL:1 MANE Select	c.102+15491C>A		intron	N/A	ENSP00000370194.4	O60547-1
	GMDS	ENST00000950953.1		c.102+15491C>A		intron	N/A	ENSP00000621012.1
	GMDS	ENST00000851213.1		c.102+15491C>A		intron	N/A	ENSP00000521272.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16784 AN: 151956 Hom.: 1025 Cov.: 32

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.110 AC: 16784 AN: 152076 Hom.: 1022 Cov.: 32 AF XY: 0.114 AC XY: 8447 AN XY: 74322

African (AFR) AF: 0.0776 AC: 3223 AN: 41508

American (AMR) AF: 0.0999 AC: 1526 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3468

East Asian (EAS) AF: 0.178 AC: 918 AN: 5156

South Asian (SAS) AF: 0.165 AC: 792 AN: 4808

European-Finnish (FIN) AF: 0.158 AC: 1663 AN: 10550

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7673 AN: 67988

Other (OTH) AF: 0.126 AC: 267 AN: 2112

Alfa AF: 0.112 Hom.: 629

Bravo AF: 0.103

Asia WGS AF: 0.176 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.39
PhyloP100		0.33
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: rs9405550; hg19: chr6-2230064;