6-119187042-C-T

Position:

• chr6-119187042-C-T

Variant summary

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

The NM_005907.4(MAN1A1):​c.1719+1363G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,986 control chromosomes in the GnomAD database, including 8,760 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 0.33 (8760 hom., cov: 32)
• Consequence: MAN1A1 NM_005907.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529

Genes affected

MAN1A1 (HGNC:6821): (mannosidase alpha class 1A member 1) This gene encodes a class I mammalian Golgi 1,2-mannosidase which is a type II transmembrane protein. This protein catalyzes the hydrolysis of three terminal mannose residues from peptide-bound Man(9)-GlcNAc(2) oligosaccharides and belongs to family 47 of glycosyl hydrolases. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -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 = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN1A1	NM_005907.4	c.1719+1363G>A		intron_variant		ENST00000368468.4	NP_005898.2
MAN1A1	XM_005266986.5	c.1968+1363G>A		intron_variant			XP_005267043.1
MAN1A1	XM_011535833.3	c.1152+1363G>A		intron_variant			XP_011534135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1A1	ENST00000368468.4	c.1719+1363G>A		intron_variant		2	NM_005907.4	ENSP00000357453.3

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50688 AN: 151866 Hom.: 8755 Cov.: 32

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.334 AC: 50730 AN: 151986 Hom.: 8760 Cov.: 32 AF XY: 0.339 AC XY: 25193 AN XY: 74288

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.333

Alfa AF: 0.300 Hom.: 9233

Bravo AF: 0.333

Asia WGS AF: 0.479 AC: 1666 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	1.2
DANN	Benign	0.52

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: rs1012509; hg19: chr6-119508207;