rs2558

Variant names:

• chr6-119179509-G-A
• rs2558
• NM_005907.4:c.*310C>T

Variant summary

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

The NM_005907.4(MAN1A1):​c.*310C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 168,098 control chromosomes in the GnomAD database, including 13,645 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 0.40 (12307 hom., cov: 32)
  • Exomes 𝑓: 0.39 (1338 hom.)
• Consequence: MAN1A1 NM_005907.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 14 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]

ENSG00000253194 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005907.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1A1	NM_005907.4	MANE Select	c.*310C>T		3_prime_UTR	Exon 13 of 13	NP_005898.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1A1	ENST00000368468.4	TSL:2 MANE Select	c.*310C>T		3_prime_UTR	Exon 13 of 13	ENSP00000357453.3
	MAN1A1	ENST00000951255.1		c.*310C>T		3_prime_UTR	Exon 14 of 14	ENSP00000621314.1
	MAN1A1	ENST00000951254.1		c.*310C>T		3_prime_UTR	Exon 13 of 13	ENSP00000621313.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60394 AN: 151850 Hom.: 12294 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.388 AC: 6256 AN: 16130 Hom.: 1338 Cov.: 0 AF XY: 0.387 AC XY: 3306 AN XY: 8552

African (AFR) AF: 0.313 AC: 152 AN: 486

American (AMR) AF: 0.346 AC: 729 AN: 2106

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 180 AN: 482

East Asian (EAS) AF: 0.374 AC: 509 AN: 1360

South Asian (SAS) AF: 0.491 AC: 598 AN: 1218

European-Finnish (FIN) AF: 0.458 AC: 368 AN: 804

Middle Eastern (MID) AF: 0.393 AC: 22 AN: 56

European-Non Finnish (NFE) AF: 0.382 AC: 3396 AN: 8886

Other (OTH) AF: 0.413 AC: 302 AN: 732

GnomAD4 genome AF: 0.398 AC: 60453 AN: 151968 Hom.: 12307 Cov.: 32 AF XY: 0.401 AC XY: 29794 AN XY: 74242

African (AFR) AF: 0.340 AC: 14096 AN: 41454

American (AMR) AF: 0.365 AC: 5581 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1424 AN: 3472

East Asian (EAS) AF: 0.435 AC: 2246 AN: 5168

South Asian (SAS) AF: 0.554 AC: 2670 AN: 4822

European-Finnish (FIN) AF: 0.491 AC: 5178 AN: 10538

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27857 AN: 67920

Other (OTH) AF: 0.391 AC: 824 AN: 2106

Alfa AF: 0.402 Hom.: 14607

Bravo AF: 0.387

Asia WGS AF: 0.461 AC: 1604 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.7
DANN	Benign	0.77
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2558; hg19: chr6-119500674;