1-25617963-C-G

Variant names:

• chr1-25617963-C-G
• rs2982320
• NM_020379.4:c.166C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020379.4(MAN1C1):​c.166C>G​(p.Pro56Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,608,838 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (68 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (75 hom.)
• Consequence: MAN1C1 NM_020379.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.139
• Publications: 3 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016571283).
• BP6: Variant 1-25617963-C-G is Benign according to our data. Variant chr1-25617963-C-G is described in ClinVar as Benign. ClinVar VariationId is 782680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0566 is higher than 0.05.

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.166C>G	p.Pro56Ala	missense	Exon 1 of 12	NP_065112.1	Q9NR34
	MAN1C1	NM_001385182.1		c.166C>G	p.Pro56Ala	missense	Exon 1 of 13	NP_001372111.1
	MAN1C1	NM_001385183.1		c.166C>G	p.Pro56Ala	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.166C>G	p.Pro56Ala	missense	Exon 1 of 12	ENSP00000363452.4	Q9NR34
	MAN1C1	ENST00000899084.1		c.166C>G	p.Pro56Ala	missense	Exon 1 of 12	ENSP00000569143.1
	MAN1C1	ENST00000929760.1		c.166C>G	p.Pro56Ala	missense	Exon 1 of 11	ENSP00000599819.1

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2564 AN: 152204 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00693

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: 0.000147

Gnomad OTH AF: 0.00907

GnomAD2 exomes AF: 0.00415 AC: 997 AN: 240378 AF XY: 0.00317

Gnomad AFR exome AF: 0.0601

Gnomad AMR exome AF: 0.00296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000840

Gnomad OTH exome AF: 0.00188

GnomAD4 exome AF: 0.00169 AC: 2467 AN: 1456516 Hom.: 75 Cov.: 31 AF XY: 0.00148 AC XY: 1069 AN XY: 724618

African (AFR) AF: 0.0598 AC: 1961 AN: 32788

American (AMR) AF: 0.00347 AC: 154 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39146

South Asian (SAS) AF: 0.000163 AC: 14 AN: 85776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52240

Middle Eastern (MID) AF: 0.00244 AC: 14 AN: 5742

European-Non Finnish (NFE) AF: 0.0000685 AC: 76 AN: 1110230

Other (OTH) AF: 0.00412 AC: 248 AN: 60200

GnomAD4 genome AF: 0.0169 AC: 2567 AN: 152322 Hom.: 68 Cov.: 32 AF XY: 0.0164 AC XY: 1221 AN XY: 74486

African (AFR) AF: 0.0585 AC: 2432 AN: 41568

American (AMR) AF: 0.00692 AC: 106 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68012

Other (OTH) AF: 0.00898 AC: 19 AN: 2116

Alfa AF: 0.000954 Hom.: 1

Bravo AF: 0.0194

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0538 AC: 236

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00506 AC: 613

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.14
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.071
Sift	Uncertain	0.016	D
Sift4G	Benign	0.47	T
Polyphen		0.0030	B
Vest4		0.17
MVP		0.74
MPC		0.50
ClinPred		0.0014	T
GERP RS		1.5
PromoterAI		0.053	Neutral
Varity_R		0.041
gMVP		0.32
Mutation Taster		=98/2	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: rs2982320; hg19: chr1-25944454;