3-195750920-G-C

Position:

• chr3-195750920-G-C

Variant summary

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

The NM_018406.7(MUC4):​c.15840C>G​(p.Ile5280Met) 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. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426

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=0.11008686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUC4	NM_018406.7	c.15840C>G	p.Ile5280Met	missense_variant	23/25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.3132C>G	p.Ile1044Met	missense_variant	22/24		NP_004523.3
MUC4	NM_138297.5	c.2979C>G	p.Ile993Met	missense_variant	21/23		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.15840C>G	p.Ile5280Met	missense_variant	23/25	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000137 AC: 2 AN: 1461708 Hom.: 0 Cov.: 68 AF XY: 0.00000138 AC XY: 1 AN XY: 727156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.78
Eigen	Benign	-0.014
Eigen_PC	Benign	-0.033
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.70	T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.73	T
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.071
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.89	P;P;B;B
Vest4		0.22
MutPred		0.26		.;.;Gain of disorder (P = 0.044);.;
MVP		0.076
ClinPred		0.30	T
GERP RS		3.0
gMVP		0.39

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: rs2291652; hg19: chr3-195477791;