1-25617939-C-A

Variant names:

• chr1-25617939-C-A
• NM_020379.4:c.142C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020379.4(MAN1C1):​c.142C>A​(p.Arg48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R48L) has been classified 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: 1.65

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.142C>A	p.Arg48Ser	missense_variant	Exon 1 of 12	ENST00000374332.9	NP_065112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN1C1	ENST00000374332.9	c.142C>A	p.Arg48Ser	missense_variant	Exon 1 of 12	1	NM_020379.4	ENSP00000363452.4
MAN1C1	ENST00000263979	c.-524C>A		5_prime_UTR_variant	Exon 1 of 13	5		ENSP00000263979.3
MAN1C1	ENST00000611903	c.-489C>A		5_prime_UTR_variant	Exon 1 of 14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.142C>A (p.R48S) alteration is located in exon 1 (coding exon 1) of the MAN1C1 gene. This alteration results from a C to A substitution at nucleotide position 142, causing the arginine (R) at amino acid position 48 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.59
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.15	T
Polyphen		0.92	P
Vest4		0.26
MutPred		0.65		Gain of helix (P = 0.0164);
MVP		0.92
MPC		1.3
ClinPred		0.80	D
GERP RS		4.0
Varity_R		0.24
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-25944430;