1-25617801-C-T

Variant names:

• chr1-25617801-C-T
• NM_020379.4:c.4C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020379.4(MAN1C1):​c.4C>T​(p.Leu2Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAN1C1 NM_020379.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.619

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3543318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.4C>T	p.Leu2Phe	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.4C>T	p.Leu2Phe	missense_variant	Exon 1 of 12	1	NM_020379.4	ENSP00000363452.4
MAN1C1	ENST00000611903	c.-627C>T		5_prime_UTR_variant	Exon 1 of 14
MAN1C1	ENST00000263979.7	c.-662C>T		upstream_gene_variant		5		ENSP00000263979.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443900 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718060

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

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 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4C>T (p.L2F) alteration is located in exon 1 (coding exon 1) of the MAN1C1 gene. This alteration results from a C to T substitution at nucleotide position 4, causing the leucine (L) at amino acid position 2 to be replaced by a phenylalanine (F). 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	Benign	0.067
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.54	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.32	D
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.19	N
REVEL	Uncertain	0.31
Sift	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.15		Loss of ubiquitination at K5 (P = 0.1375);
MVP		0.75
MPC		0.66
ClinPred		0.69	D
GERP RS		2.4
Varity_R		0.096
gMVP		0.37

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: chr1-25944292;