rs2259292

Variant names:

• chr3-195774278-C-A
• NM_018406.7:c.12971G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-195774278-C-A
• chr3-195774278-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018406.7(MUC4):​c.12971G>T​(p.Gly4324Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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. G4324D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

Genes affected

MUC4 (HGNC:7514): (mucin 4, cell surface associated) The major constituents of mucus, the viscous secretion that covers epithelial surfaces such as those in the trachea, colon, and cervix, are highly glycosylated proteins called mucins. These glycoproteins play important roles in the protection of the epithelial cells and have been implicated in epithelial renewal and differentiation. This gene encodes an integral membrane glycoprotein found on the cell surface, although secreted isoforms may exist. At least two dozen transcript variants of this gene have been found, although for many of them the full-length transcript has not been determined or they are found only in tumor tissues. This gene contains a region in the coding sequence which has a variable number (>100) of 48 nt tandem repeats. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.088332295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7	c.12971G>T	p.Gly4324Val	missense_variant	Exon 4 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.263G>T	p.Gly88Val	missense_variant	Exon 3 of 24		NP_004523.3
MUC4	NM_138297.5	c.110G>T	p.Gly37Val	missense_variant	Exon 2 of 23		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.12971G>T	p.Gly4324Val	missense_variant	Exon 4 of 25	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428756 Hom.: 0 Cov.: 55 AF XY: 0.00000141 AC XY: 1 AN XY: 709246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.5
DANN	Benign	0.85
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.31	T;T;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.088	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.4	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.20	T;T;T;T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.040	B;B;.;.
Vest4		0.21
MVP		0.12
ClinPred		0.12	T
GERP RS		-2.1
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-195501149;