rs1438663

chr5-109692150-C-T

Variant summary

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

The NM_002372.4(MAN2A1):c.135+1598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,130 control chromosomes in the GnomAD database, including 2,702 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 0.18 (2702 hom., cov: 32)
• Consequence: MAN2A1 NM_002372.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN2A1	NM_002372.4	c.135+1598C>T		intron_variant		ENST00000261483.5
MAN2A1	XM_011543395.4	c.135+1598C>T		intron_variant
MAN2A1	XM_017009472.2	c.-13+248C>T		intron_variant
MAN2A1	XR_007058604.1	n.626+1598C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN2A1	ENST00000261483.5	c.135+1598C>T		intron_variant		1	NM_002372.4	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27762 AN: 152012 Hom.: 2694 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.183 AC: 27805 AN: 152130 Hom.: 2702 Cov.: 32 AF XY: 0.178 AC XY: 13206 AN XY: 74384

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0328

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.164

Alfa AF: 0.177 Hom.: 1223

Bravo AF: 0.182

Asia WGS AF: 0.103 AC: 359 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	3.5
Dann	Benign	0.15

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: rs1438663; hg19: chr5-109027851;