ENST00000597692.1:n.*91C>A

Variant names:

• chr19-12646529-G-T
• rs145108101
• ENST00000597692.1:n.*91C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000597692.1(ENSG00000269242):​n.*91C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 855,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ENSG00000269242 ENST00000597692.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 0 publications found

Genes affected

ENSG00000269242 (HGNC:):

MAN2B1 (HGNC:6826): (mannosidase alpha class 2B member 1) This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

MAN2B1 Gene-Disease associations (from GenCC):

• alpha-mannosidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Myriad Women’s Health, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2B1	NM_000528.4	c.*91C>A		3_prime_UTR_variant	Exon 24 of 24	ENST00000456935.7	NP_000519.2
MAN2B1	NM_001440570.1	c.*91C>A		3_prime_UTR_variant	Exon 24 of 24		NP_001427499.1
MAN2B1	NM_001173498.2	c.*91C>A		3_prime_UTR_variant	Exon 24 of 24		NP_001166969.1
MAN2B1	XM_047438841.1	c.*91C>A		3_prime_UTR_variant	Exon 17 of 17		XP_047294797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000269242	ENST00000597692.1	n.*91C>A		non_coding_transcript_exon_variant	Exon 4 of 5	2		ENSP00000470240.1
MAN2B1	ENST00000456935.7	c.*91C>A		3_prime_UTR_variant	Exon 24 of 24	1	NM_000528.4	ENSP00000395473.2
ENSG00000269242	ENST00000597692.1	n.*91C>A		3_prime_UTR_variant	Exon 4 of 5	2		ENSP00000470240.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000351 AC: 3 AN: 855238 Hom.: 0 Cov.: 12 AF XY: 0.00000672 AC XY: 3 AN XY: 446492

African (AFR) AF: 0.00 AC: 0 AN: 21670

American (AMR) AF: 0.00 AC: 0 AN: 38956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21946

East Asian (EAS) AF: 0.00 AC: 0 AN: 36244

South Asian (SAS) AF: 0.00 AC: 0 AN: 72332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4668

European-Non Finnish (NFE) AF: 0.00000529 AC: 3 AN: 567396

Other (OTH) AF: 0.00 AC: 0 AN: 40452

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.75
PhyloP100		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145108101; hg19: chr19-12757343;