Genetic Variant MUCL1:p.Pro36Ser (chr12-54856775-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_058173.3(MUCL1):c.106C>T(p.Pro36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,459,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 0.000012 ( 0 hom. )

Consequence

MUCL1
NM_058173.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.983

Variant links:

Genes affected

MUCL1 (HGNC:30588): (mucin like 1) Predicted to be located in Golgi lumen and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MUCL1 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=0.11987835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUCL1	NM_058173.3 link	c.106C>T	p.Pro36Ser	missense_variant	Exon 3 of 4	ENST00000308796.11	NP_477521.1	Q96DR8
MUCL1	XM_047428272.1 link	c.106C>T	p.Pro36Ser	missense_variant	Exon 4 of 5		XP_047284228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MUCL1	ENST00000308796.11 link	c.106C>T	p.Pro36Ser	missense_variant	Exon 3 of 4	1	NM_058173.3	ENSP00000311364.5	Q96DR8
MUCL1	ENST00000546809.5 link	c.91C>T	p.Pro31Ser	missense_variant	Exon 3 of 4	3		ENSP00000449369.1	F8VV13
MUCL1	ENST00000547990.1 link	n.405C>T		non_coding_transcript_exon_variant	Exon 3 of 4	4
MUCL1	ENST00000652289.1 link	n.406C>T		non_coding_transcript_exon_variant	Exon 3 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

241054

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130630

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:

0.0000282

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1459142

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106C>T (p.P36S) alteration is located in exon 3 (coding exon 3) of the MUCL1 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the proline (P) at amino acid position 36 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

Benign

0.097

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.28

DANN

Benign

0.31

DEOGEN2

Benign

0.091

T;T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.42

T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-8.0

D;D;.

REVEL

Benign

0.047

Sift

Pathogenic

0.0

D;D;.

Sift4G

Benign

0.35

T;T;T

Polyphen

0.71

.;P;.

Vest4

0.11

MutPred

0.21

.;Gain of catalytic residue at Y31 (P = 0.0085);Gain of catalytic residue at Y31 (P = 0.0085);

MVP

0.014

MPC

0.0030

ClinPred

0.85

GERP RS

-4.0

Varity_R

0.068

gMVP

0.071

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