rs17162094

Variant names:

• chr5-109704072-G-T
• rs17162094
• NM_002372.4:c.136-9448G>T

Variant summary

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

The NM_002372.4(MAN2A1):​c.136-9448G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 152,238 control chromosomes in the GnomAD database, including 224 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 0.054 (224 hom., cov: 32)
• Consequence: MAN2A1 NM_002372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 4 publications found

Genes affected

MAN2A1 (HGNC:6824): (mannosidase alpha class 2A member 1) This gene encodes a glycosyl hydrolase that localizes to the Golgi and catalyzes the final hydrolytic step in the asparagine-linked oligosaccharide (N-glycan) maturation pathway. Mutations in the mouse homolog of this gene have been shown to cause a systemic autoimmune disease similar to human systemic lupus erythematosus. [provided by RefSeq, Dec 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2A1	NM_002372.4	c.136-9448G>T		intron_variant	Intron 1 of 21	ENST00000261483.5	NP_002363.2
MAN2A1	XM_017009472.2	c.-12-9448G>T		intron_variant	Intron 1 of 21		XP_016864961.1
MAN2A1	XM_011543395.4	c.136-9448G>T		intron_variant	Intron 1 of 16		XP_011541697.1
MAN2A1	XR_007058604.1	n.627-9448G>T		intron_variant	Intron 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN2A1	ENST00000261483.5	c.136-9448G>T		intron_variant	Intron 1 of 21	1	NM_002372.4	ENSP00000261483.4

Frequencies

GnomAD3 genomes AF: 0.0537 AC: 8162 AN: 152120 Hom.: 223 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.0727

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0535

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

GnomAD4 genome AF: 0.0536 AC: 8165 AN: 152238 Hom.: 224 Cov.: 32 AF XY: 0.0522 AC XY: 3886 AN XY: 74420

African (AFR) AF: 0.0480 AC: 1993 AN: 41542

American (AMR) AF: 0.0358 AC: 548 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0727 AC: 252 AN: 3468

East Asian (EAS) AF: 0.0278 AC: 144 AN: 5178

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4826

European-Finnish (FIN) AF: 0.0584 AC: 619 AN: 10602

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4368 AN: 68016

Other (OTH) AF: 0.0529 AC: 112 AN: 2116

Alfa AF: 0.0595 Hom.: 434

Bravo AF: 0.0527

Asia WGS AF: 0.0280 AC: 98 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.57
PhyloP100		0.33
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: rs17162094; hg19: chr5-109039773;