Genetic Variant MUCL1:p.Pro74Leu (chr12-54856890-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_058173.3(MUCL1):c.221C>T(p.Pro74Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

MUCL1
NM_058173.3 missense, splice_region

Scores

Splicing: ADA: 0.01173

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.18

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059789866).

BP6

Variant 12-54856890-C-T is Benign according to our data. Variant chr12-54856890-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3875875.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058173.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUCL1	NM_058173.3	MANE Select	c.221C>T	p.Pro74Leu	missense splice_region	Exon 3 of 4	NP_477521.1	Q96DR8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MUCL1	ENST00000308796.11	TSL:1 MANE Select	c.221C>T	p.Pro74Leu	missense splice_region	Exon 3 of 4	ENSP00000311364.5	Q96DR8
MUCL1	ENST00000546809.5	TSL:3	c.206C>T	p.Pro69Leu	missense splice_region	Exon 3 of 4	ENSP00000449369.1	F8VV13
MUCL1	ENST00000547990.1	TSL:4	n.520C>T		splice_region non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248328

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461452

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.0000224

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1111766

Other (OTH)

AF:

0.0000166

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

4.4

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.026

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.41

M_CAP

Benign

0.00052

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.0

PhyloP100

-2.2

PrimateAI

Benign

0.20

PROVEAN

Benign

2.2

REVEL

Benign

0.031

Sift

Benign

1.0

Sift4G

Uncertain

0.034

Polyphen

0.0

Vest4

0.058

MutPred

0.34

Gain of catalytic residue at P74 (P = 0.004)

MVP

0.11

MPC

0.0030

ClinPred

0.035

GERP RS

-5.8

Varity_R

0.018

gMVP

0.030

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.012

dbscSNV1_RF

Benign

0.41

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over