chr3-195787862-C-T

Variant names:

• chr3-195787862-C-T
• rs201433788
• NM_018406.7:c.3718G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018406.7(MUC4):​c.3718G>A​(p.Ala1240Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 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. A1240S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• Publications: 5 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05823353).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	NM_018406.7	MANE Select	c.3718G>A	p.Ala1240Thr	missense	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-9407G>A		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-13557G>A		intron	N/A	NP_612154.2	Q99102-12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	ENST00000463781.8	TSL:5 MANE Select	c.3718G>A	p.Ala1240Thr	missense	Exon 2 of 25	ENSP00000417498.3	Q99102-1
	MUC4	ENST00000346145.8	TSL:1	c.83-9407G>A		intron	N/A	ENSP00000304207.6	Q99102-13
	MUC4	ENST00000349607.8	TSL:1	c.83-13557G>A		intron	N/A	ENSP00000338109.4	Q99102-12

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 2338 Hom.: 0 Cov.: 0

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

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000264 AC: 1 AN: 378574 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 198358

⚠️ 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: 8664

American (AMR) AF: 0.00 AC: 0 AN: 16794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11348

East Asian (EAS) AF: 0.00 AC: 0 AN: 27750

South Asian (SAS) AF: 0.00 AC: 0 AN: 38496

European-Finnish (FIN) AF: 0.0000423 AC: 1 AN: 23652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 229930

Other (OTH) AF: 0.00 AC: 0 AN: 20610

⚠️ 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 AF: 0.00 AC: 0 AN: 2338 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1114

African (AFR) AF: 0.00 AC: 0 AN: 162

American (AMR) AF: 0.00 AC: 0 AN: 368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 84

East Asian (EAS) AF: 0.00 AC: 0 AN: 104

South Asian (SAS) AF: 0.00 AC: 0 AN: 92

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1298

Other (OTH) AF: 0.00 AC: 0 AN: 28

Alfa AF: 0.00 Hom.: 308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.21
DANN	Benign	0.90
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00028	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.10
Sift	Benign	0.21	T
Sift4G	Uncertain	0.024	D
Vest4		0.066
MutPred		0.14		Gain of glycosylation at A1240 (P = 0.0062)
MVP		0.014
ClinPred		0.064	T
gMVP		0.000035
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: rs201433788; hg19: chr3-195514733;