chr1-25618279-C-T

Variant names:

• chr1-25618279-C-T
• NM_020379.4:c.482C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020379.4(MAN1C1):​c.482C>T​(p.Ala161Val) 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. 15/21 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAN1C1 NM_020379.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.659

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06320736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN1C1	NM_020379.4	c.482C>T	p.Ala161Val	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.482C>T	p.Ala161Val	missense_variant	Exon 1 of 12	1	NM_020379.4	ENSP00000363452.4
MAN1C1	ENST00000263979	c.-184C>T		5_prime_UTR_variant	Exon 1 of 13	5		ENSP00000263979.3
MAN1C1	ENST00000611903	c.-149C>T		5_prime_UTR_variant	Exon 1 of 14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1451662 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 721162

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: 0.00

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

Apr 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482C>T (p.A161V) 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 482, causing the alanine (A) at amino acid position 161 to be replaced by a valine (V). 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	0.079
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.12
Sift	Benign	0.32	T
Sift4G	Benign	0.27	T
Polyphen		0.0010	B
Vest4		0.050
MutPred		0.25		Gain of MoRF binding (P = 0.1182);
MVP		0.79
MPC		0.50
ClinPred		0.056	T
GERP RS		0.093
Varity_R		0.031
gMVP		0.34

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: chr1-25944770;