NM_058173.3:c.140C>A

Variant names:

• chr12-54856809-C-A
• rs759721973
• NM_058173.3:c.140C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_058173.3(MUCL1):​c.140C>A​(p.Thr47Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T47S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MUCL1 NM_058173.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 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 (REVEL=0.028).

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.140C>A	p.Thr47Asn	missense	Exon 3 of 4	NP_477521.1	Q96DR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUCL1	ENST00000308796.11	TSL:1 MANE Select	c.140C>A	p.Thr47Asn	missense	Exon 3 of 4	ENSP00000311364.5	Q96DR8
	MUCL1	ENST00000546809.5	TSL:3	c.125C>A	p.Thr42Asn	missense	Exon 3 of 4	ENSP00000449369.1	F8VV13
	MUCL1	ENST00000547990.1	TSL:4	n.439C>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460266 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 726430

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110980

Other (OTH) AF: 0.00 AC: 0 AN: 60286

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.23
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.030	N
M_CAP	Benign	0.00092	T
PhyloP100		-1.7
ClinPred		0.93	D
GERP RS		-0.13
Varity_R		0.23
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs759721973; hg19: chr12-55250593;