rs3800036

Positions:

• chr6-1760322-G-A

Variant summary

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

The NM_001500.4(GMDS):​c.772-17736C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,072 control chromosomes in the GnomAD database, including 20,437 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 0.52 (20437 hom., cov: 32)
• Consequence: GMDS NM_001500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456

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]

LOC124901239 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMDS	NM_001500.4	c.772-17736C>T		intron_variant		ENST00000380815.5	NP_001491.1
LOC124901239	XR_007059404.1	n.5290C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMDS	ENST00000380815.5	c.772-17736C>T		intron_variant		1	NM_001500.4	ENSP00000370194	P1
GMDS	ENST00000530927.5	c.682-17736C>T		intron_variant		1		ENSP00000436726
GMDS	ENST00000380805.6	n.898-17736C>T		intron_variant, non_coding_transcript_variant		2
GMDS	ENST00000531690.5	n.251-17736C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78370 AN: 151954 Hom.: 20424 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.516 AC: 78420 AN: 152072 Hom.: 20437 Cov.: 32 AF XY: 0.524 AC XY: 38970 AN XY: 74354

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.526

Alfa AF: 0.527 Hom.: 44319

Bravo AF: 0.504

Asia WGS AF: 0.655 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.48

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: rs3800036; hg19: chr6-1760556;