1-25749278-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_020379.4(MAN1C1):c.777G>A(p.Glu259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,612,590 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (6 hom.)
• Consequence: MAN1C1 NM_020379.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.33

Genes affected

MAN1C1 (HGNC:19080): (mannosidase alpha class 1C member 1) Predicted to enable mannosyl-oligosaccharide 1,2-alpha-mannosidase activity. Predicted to be involved in N-glycan processing. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-25749278-G-A is Benign according to our data. Variant chr1-25749278-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638501.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.33 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN1C1	NM_020379.4	c.777G>A	p.Glu259=	synonymous_variant	4/12	ENST00000374332.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAN1C1	ENST00000374332.9	c.777G>A	p.Glu259=	synonymous_variant	4/12	1	NM_020379.4	P1
MAN1C1	ENST00000263979.7	c.237G>A	p.Glu79=	synonymous_variant	5/13	5
MAN1C1	ENST00000374329.1	c.90G>A	p.Glu30=	synonymous_variant	3/11	2
MAN1C1	ENST00000473891.1	n.175G>A		non_coding_transcript_exon_variant	3/5	4

Frequencies

GnomAD3 genomes AF: 0.000913 AC: 139 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00122 AC: 303 AN: 248920 Hom.: 1 AF XY: 0.00137 AC XY: 184 AN XY: 134342

Gnomad AFR exome AF: 0.000438

Gnomad AMR exome AF: 0.00160

Gnomad ASJ exome AF: 0.00291

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00151

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00136

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00108 AC: 1570 AN: 1460304 Hom.: 6 Cov.: 30 AF XY: 0.00115 AC XY: 834 AN XY: 726164

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.00182

Gnomad4 ASJ exome AF: 0.00315

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00137

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000987

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.000913 AC: 139 AN: 152286 Hom.: 0 Cov.: 33 AF XY: 0.000860 AC XY: 64 AN XY: 74448

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.00127

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MAN1C1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	6.8
Dann	Benign	0.60

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: rs146745645; hg19: chr1-26075769;