6-119203519-T-C

Variant names:

• chr6-119203519-T-C
• rs9489621
• NM_005907.4:c.1116+1240A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005907.4(MAN1A1):​c.1116+1240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,590 control chromosomes in the GnomAD database, including 19,721 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 0.50 (19721 hom., cov: 29)
• Consequence: MAN1A1 NM_005907.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 1 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 (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1A1	NM_005907.4	c.1116+1240A>G		intron_variant	Intron 7 of 12	ENST00000368468.4	NP_005898.2
MAN1A1	XM_005266986.5	c.1365+1240A>G		intron_variant	Intron 7 of 12		XP_005267043.1
MAN1A1	XM_011535833.3	c.549+1240A>G		intron_variant	Intron 6 of 11		XP_011534135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1A1	ENST00000368468.4	c.1116+1240A>G		intron_variant	Intron 7 of 12	2	NM_005907.4	ENSP00000357453.3

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75439 AN: 151472 Hom.: 19711 Cov.: 29

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.498 AC: 75481 AN: 151590 Hom.: 19721 Cov.: 29 AF XY: 0.495 AC XY: 36659 AN XY: 74054

African (AFR) AF: 0.396 AC: 16332 AN: 41272

American (AMR) AF: 0.393 AC: 5988 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1963 AN: 3466

East Asian (EAS) AF: 0.278 AC: 1418 AN: 5100

South Asian (SAS) AF: 0.380 AC: 1824 AN: 4800

European-Finnish (FIN) AF: 0.633 AC: 6660 AN: 10524

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39679 AN: 67884

Other (OTH) AF: 0.479 AC: 1010 AN: 2110

Alfa AF: 0.526 Hom.: 7287

Bravo AF: 0.472

Asia WGS AF: 0.344 AC: 1195 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	3.7
DANN	Benign	0.80
PhyloP100		0.51
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: rs9489621; hg19: chr6-119524684;