Variant 1-25618314-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020379.4(MAN1C1):c.517G>A(p.Ala173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000345 in 1,449,768 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000034 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.829

Variant links:

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]

MAN1C1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09110215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAN1C1	NM_020379.4 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	1/12	ENST00000374332.9	NP_065112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1C1	ENST00000374332.9 linkuse as main transcript	c.517G>A	p.Ala173Thr	missense_variant	1/12	1	NM_020379.4	ENSP00000363452	P1
MAN1C1	ENST00000263979.7 linkuse as main transcript	c.-149G>A		5_prime_UTR_variant	1/13	5		ENSP00000263979

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000903

AC:

AN:

221444

Hom.:

AF XY:

0.00000825

AC XY:

AN XY:

121240

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000345

AC:

AN:

1449768

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

720142

show subpopulations

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:

0.0000424

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.517G>A (p.A173T) alteration is located in exon 1 (coding exon 1) of the MAN1C1 gene. This alteration results from a G to A substitution at nucleotide position 517, causing the alanine (A) at amino acid position 173 to be replaced by a threonine (T). 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

0.068

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.29

M_CAP

Benign

0.055

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.73

REVEL

Benign

0.22

Sift

Benign

0.19

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.044

MutPred

0.55

Gain of loop (P = 0.0166);

MVP

0.74

MPC

0.49

ClinPred

0.085

GERP RS

3.2

Varity_R

0.082

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over