chr1-25618237-C-G

Variant names:

• chr1-25618237-C-G
• rs1299672770
• NM_020379.4:c.440C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020379.4(MAN1C1):​c.440C>G​(p.Ala147Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,602,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: MAN1C1 NM_020379.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00300
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080629766).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020379.4. 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
	MAN1C1	NM_020379.4	MANE Select	c.440C>G	p.Ala147Gly	missense	Exon 1 of 12	NP_065112.1	Q9NR34
	MAN1C1	NM_001385182.1		c.440C>G	p.Ala147Gly	missense	Exon 1 of 13	NP_001372111.1
	MAN1C1	NM_001385183.1		c.440C>G	p.Ala147Gly	missense	Exon 1 of 12	NP_001372112.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN1C1	ENST00000374332.9	TSL:1 MANE Select	c.440C>G	p.Ala147Gly	missense	Exon 1 of 12	ENSP00000363452.4	Q9NR34
	MAN1C1	ENST00000899084.1		c.440C>G	p.Ala147Gly	missense	Exon 1 of 12	ENSP00000569143.1
	MAN1C1	ENST00000929760.1		c.440C>G	p.Ala147Gly	missense	Exon 1 of 11	ENSP00000599819.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000453 AC: 1 AN: 220796 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1449904 Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9 AN XY: 720324

African (AFR) AF: 0.00 AC: 0 AN: 33174

American (AMR) AF: 0.00 AC: 0 AN: 42704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25862

East Asian (EAS) AF: 0.00 AC: 0 AN: 39128

South Asian (SAS) AF: 0.00 AC: 0 AN: 84118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1108406

Other (OTH) AF: 0.0000167 AC: 1 AN: 60020

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.0030
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.18
Sift	Benign	0.47	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.079
MutPred		0.38		Gain of loop (P = 0.0111)
MVP		0.78
MPC		0.51
ClinPred		0.043	T
GERP RS		2.6
PromoterAI		-0.021	Neutral
Varity_R		0.042
gMVP		0.26
Mutation Taster		=90/10	polymorphism

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: rs1299672770; hg19: chr1-25944728;