12-54856821-C-G

Position:

• chr12-54856821-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The ENST00000308796.11(MUCL1):​c.152C>G​(p.Thr51Ser) 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. 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: 31)
• Consequence: MUCL1 ENST00000308796.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.625

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a glycosylation_site O-linked (GalNAc...) threonine (size 0) in uniprot entity MUCL1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097791016).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUCL1	NM_058173.3	c.152C>G	p.Thr51Ser	missense_variant	3/4	ENST00000308796.11	NP_477521.1
MUCL1	XM_047428272.1	c.152C>G	p.Thr51Ser	missense_variant	4/5		XP_047284228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUCL1	ENST00000308796.11	c.152C>G	p.Thr51Ser	missense_variant	3/4	1	NM_058173.3	ENSP00000311364	P1
MUCL1	ENST00000546809.5	c.137C>G	p.Thr46Ser	missense_variant	3/4	3		ENSP00000449369
MUCL1	ENST00000547990.1	n.451C>G		non_coding_transcript_exon_variant	3/4	4
MUCL1	ENST00000652289.1	n.452C>G		non_coding_transcript_exon_variant	3/5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.152C>G (p.T51S) alteration is located in exon 3 (coding exon 3) of the MUCL1 gene. This alteration results from a C to G substitution at nucleotide position 152, causing the threonine (T) at amino acid position 51 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	0.22
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.19
DEOGEN2	Benign	0.087	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.30	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.7	D;N
REVEL	Benign	0.0080
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.077	T;T
Polyphen		0.050	.;B
Vest4		0.078
MutPred		0.20		.;Gain of catalytic residue at T52 (P = 0.0199);
MVP		0.014
MPC		0.0033
ClinPred		0.48	T
GERP RS		0.42
Varity_R		0.12
gMVP		0.068

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

Other links and lift over

dbSNP: rs1868303515; hg19: chr12-55250605;