3-195785701-G-A

Variant names:

• chr3-195785701-G-A
• rs558165743
• NM_018406.7:c.5879C>T

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.5879C>T​(p.Ser1960Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,260,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.0 (0 hom., cov: 50)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 0 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=0.035728008).

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.5879C>T	p.Ser1960Leu	missense	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-7246C>T		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-11396C>T		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.5879C>T	p.Ser1960Leu	missense	Exon 2 of 25	ENSP00000417498.3
	MUC4	ENST00000346145.8	TSL:1	c.83-7246C>T		intron	N/A	ENSP00000304207.6
	MUC4	ENST00000349607.8	TSL:1	c.83-11396C>T		intron	N/A	ENSP00000338109.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 140064 Hom.: 0 Cov.: 50

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 161004 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1260436 Hom.: 0 Cov.: 251 AF XY: 0.00 AC XY: 0 AN XY: 622934

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28184

American (AMR) AF: 0.00 AC: 0 AN: 30490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21164

East Asian (EAS) AF: 0.00 AC: 0 AN: 30324

South Asian (SAS) AF: 0.00 AC: 0 AN: 72574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3954

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 977114

Other (OTH) AF: 0.00 AC: 0 AN: 51312

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 140160 Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0 AN XY: 68720

African (AFR) AF: 0.00 AC: 0 AN: 35542

American (AMR) AF: 0.00 AC: 0 AN: 14364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3278

East Asian (EAS) AF: 0.00 AC: 0 AN: 5024

South Asian (SAS) AF: 0.00 AC: 0 AN: 4578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64272

Other (OTH) AF: 0.00 AC: 0 AN: 1952

ExAC AF: 0.0000220 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.94
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.020
Sift	Benign	0.049	D
Sift4G	Benign	1.0	T
Vest4		0.097
MutPred		0.20		Loss of glycosylation at S1960 (P = 0.0051)
MVP		0.030
ClinPred		0.083	T
GERP RS		-0.041
gMVP		0.00020
Mutation Taster		=100/0	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: rs558165743; hg19: chr3-195512572;