chr3-195778793-G-C

Variant names:

• chr3-195778793-G-C
• rs2688513
• NM_018406.7:c.12787C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018406.7(MUC4):​c.12787C>G​(p.Pro4263Ala) 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. 15/20 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: 34)
  • Exomes 𝑓: 0.0000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 43 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061398327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018406.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	NM_018406.7	MANE Select	c.12787C>G	p.Pro4263Ala	missense	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-338C>G		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-4488C>G		intron	N/A	NP_612154.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	ENST00000463781.8	TSL:5 MANE Select	c.12787C>G	p.Pro4263Ala	missense	Exon 2 of 25	ENSP00000417498.3
	MUC4	ENST00000308466.12	TSL:1	n.16C>G		non_coding_transcript_exon	Exon 1 of 23	ENSP00000310528.8
	MUC4	ENST00000339251.9	TSL:1	n.16C>G		non_coding_transcript_exon	Exon 1 of 24	ENSP00000345378.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000418 AC: 6 AN: 1434326 Hom.: 0 Cov.: 66 AF XY: 0.00000561 AC XY: 4 AN XY: 713418

African (AFR) AF: 0.00 AC: 0 AN: 30334

American (AMR) AF: 0.00 AC: 0 AN: 43484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25834

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 84756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000457 AC: 5 AN: 1093044

Other (OTH) AF: 0.00 AC: 0 AN: 59456

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 108414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.082
DANN	Benign	0.62
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.29
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.049
Sift	Benign	0.15	T
Sift4G	Benign	0.21	T
Vest4		0.12
MutPred		0.14		Loss of phosphorylation at T4262 (P = 0.0842)
MVP		0.014
ClinPred		0.071	T
GERP RS		0.27
gMVP		0.049
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2688513; hg19: chr3-195505664;