6-2222768-T-G

Variant names:

• chr6-2222768-T-G
• rs9392374
• NM_001500.4:c.102+22553A>C

Variant summary

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

The NM_001500.4(GMDS):​c.102+22553A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,070 control chromosomes in the GnomAD database, including 1,262 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 0.13 (1262 hom., cov: 32)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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=-0.85).
• 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+22553A>C		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+22553A>C		intron_variant	Intron 1 of 10	1	NM_001500.4	ENSP00000370194.4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19004 AN: 151950 Hom.: 1261 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.125 AC: 19015 AN: 152070 Hom.: 1262 Cov.: 32 AF XY: 0.128 AC XY: 9508 AN XY: 74318

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.134

Alfa AF: 0.113 Hom.: 1358

Bravo AF: 0.120

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9392374; hg19: chr6-2223002;