chr1-25617837-C-T

Variant names:

• chr1-25617837-C-T
• rs781600564
• NM_020379.4:c.40C>T

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.40C>T​(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAN1C1 NM_020379.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.201
• 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=0.16681588).

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.40C>T	p.Pro14Ser	missense	Exon 1 of 12	NP_065112.1	Q9NR34
	MAN1C1	NM_001385182.1		c.40C>T	p.Pro14Ser	missense	Exon 1 of 13	NP_001372111.1
	MAN1C1	NM_001385183.1		c.40C>T	p.Pro14Ser	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.40C>T	p.Pro14Ser	missense	Exon 1 of 12	ENSP00000363452.4	Q9NR34
	MAN1C1	ENST00000899084.1		c.40C>T	p.Pro14Ser	missense	Exon 1 of 12	ENSP00000569143.1
	MAN1C1	ENST00000929760.1		c.40C>T	p.Pro14Ser	missense	Exon 1 of 11	ENSP00000599819.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.079
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	-0.0072	T
MutationAssessor	Benign	0.14	N
PhyloP100		-0.20
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.49	N
REVEL	Uncertain	0.31
Sift	Benign	0.41	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.095
MutPred		0.48		Gain of loop (P = 0.0435)
MVP		0.74
MPC		0.51
ClinPred		0.034	T
GERP RS		-1.5
PromoterAI		-0.095	Neutral
Varity_R		0.051
gMVP		0.34
Mutation Taster		=86/14	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: rs781600564; hg19: chr1-25944328;