Variant chr1-25746749-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020379.4(MAN1C1):c.719A>C(p.Lys240Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000264 in 1,452,490 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

MAN1C1
NM_020379.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
MAN1C1	NM_020379.4 linkuse as main transcript	c.719A>C	p.Lys240Thr	missense_variant	3/12	ENST00000374332.9	NP_065112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MAN1C1	ENST00000374332.9 linkuse as main transcript	c.719A>C	p.Lys240Thr	missense_variant	3/12	1	NM_020379.4	ENSP00000363452	P1
MAN1C1	ENST00000263979.7 linkuse as main transcript	c.179A>C	p.Lys60Thr	missense_variant	4/13	5		ENSP00000263979
MAN1C1	ENST00000374329.1 linkuse as main transcript	c.32A>C	p.Lys11Thr	missense_variant	2/11	2		ENSP00000363449
MAN1C1	ENST00000473891.1 linkuse as main transcript	n.117A>C		non_coding_transcript_exon_variant	2/5	4

Frequencies

GnomAD3 genomes

AF:

0.000102

AC:

AN:

136976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000235

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000139

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

250580

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000280

AC:

369

AN:

1315514

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

170

AN XY:

653824

show subpopulations

Gnomad4 AFR exome

AF:

0.000103

Gnomad4 AMR exome

AF:

0.000123

Gnomad4 ASJ exome

AF:

0.0000489

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000331

Gnomad4 OTH exome

AF:

0.000317

GnomAD4 genome

AF:

0.000102

AC:

AN:

136976

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

65648

show subpopulations

Gnomad4 AFR

AF:

0.0000550

Gnomad4 AMR

AF:

0.000235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000139

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000238

Hom.:

Bravo

AF:

0.000200

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

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

May 14, 2024

The c.719A>C (p.K240T) alteration is located in exon 3 (coding exon 3) of the MAN1C1 gene. This alteration results from a A to C substitution at nucleotide position 719, causing the lysine (K) at amino acid position 240 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

0.23

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

.;T;T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

1.8

.;L;.;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.4

.;D;D;D

REVEL

Uncertain

0.30

Sift

Benign

0.085

.;T;T;T

Sift4G

Benign

0.17

T;T;D;D

Polyphen

0.70

.;P;.;.

Vest4

0.45

MVP

0.77

MPC

0.93

ClinPred

0.16

GERP RS

4.9

Varity_R

0.43

gMVP

0.72

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