chr6-119187042-C-T

Variant names:

• chr6-119187042-C-T
• rs1012509
• NM_005907.4:c.1719+1363G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

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 = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1A1	NM_005907.4	c.1719+1363G>A		intron_variant	Intron 11 of 12	ENST00000368468.4	NP_005898.2
MAN1A1	XM_005266986.5	c.1968+1363G>A		intron_variant	Intron 11 of 12		XP_005267043.1
MAN1A1	XM_011535833.3	c.1152+1363G>A		intron_variant	Intron 10 of 11		XP_011534135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1A1	ENST00000368468.4	c.1719+1363G>A		intron_variant	Intron 11 of 12	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

African (AFR) AF: 0.374 AC: 15505 AN: 41464

American (AMR) AF: 0.317 AC: 4843 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1185 AN: 3468

East Asian (EAS) AF: 0.536 AC: 2759 AN: 5150

South Asian (SAS) AF: 0.515 AC: 2474 AN: 4806

European-Finnish (FIN) AF: 0.344 AC: 3631 AN: 10568

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19226 AN: 67928

Other (OTH) AF: 0.333 AC: 702 AN: 2106

Alfa AF: 0.302 Hom.: 11851

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
PhyloP100		-0.53
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: rs1012509; hg19: chr6-119508207;