rs201433788

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-195787862-C-A
• chr3-195787862-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_018406.7(MUC4):​c.3718G>T​(p.Ala1240Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (183 hom., cov: 0)
  • Exomes 𝑓: 0.66 (81018 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016600192).
• BP6: Variant 3-195787862-C-A is Benign according to our data. Variant chr3-195787862-C-A is described in ClinVar as Benign. ClinVar VariationId is 403124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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>T	p.Ala1240Ser	missense	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-9407G>T		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-13557G>T		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>T	p.Ala1240Ser	missense	Exon 2 of 25	ENSP00000417498.3	Q99102-1
	MUC4	ENST00000346145.8	TSL:1	c.83-9407G>T		intron	N/A	ENSP00000304207.6	Q99102-13
	MUC4	ENST00000349607.8	TSL:1	c.83-13557G>T		intron	N/A	ENSP00000338109.4	Q99102-12

Frequencies

GnomAD3 genomes AF: 0.391 AC: 890 AN: 2274 Hom.: 185 Cov.: 0

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.577

GnomAD2 exomes AF: 0.632 AC: 25717 AN: 40662 AF XY: 0.629

Gnomad AFR exome AF: 0.810

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.721

Gnomad EAS exome AF: 0.770

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.621

Gnomad OTH exome AF: 0.643

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.660 AC: 242133 AN: 366850 Hom.: 81018 Cov.: 4 AF XY: 0.658 AC XY: 126564 AN XY: 192406

African (AFR) AF: 0.826 AC: 6972 AN: 8440

American (AMR) AF: 0.546 AC: 8721 AN: 15986

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 8178 AN: 11048

East Asian (EAS) AF: 0.773 AC: 21015 AN: 27192

South Asian (SAS) AF: 0.597 AC: 22052 AN: 36956

European-Finnish (FIN) AF: 0.676 AC: 15530 AN: 22978

Middle Eastern (MID) AF: 0.637 AC: 811 AN: 1274

European-Non Finnish (NFE) AF: 0.651 AC: 145118 AN: 222988

Other (OTH) AF: 0.687 AC: 13736 AN: 19988

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.391 AC: 886 AN: 2268 Hom.: 183 Cov.: 0 AF XY: 0.387 AC XY: 416 AN XY: 1076

African (AFR) AF: 0.569 AC: 91 AN: 160

American (AMR) AF: 0.349 AC: 122 AN: 350

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 38 AN: 82

East Asian (EAS) AF: 0.396 AC: 38 AN: 96

South Asian (SAS) AF: 0.326 AC: 28 AN: 86

European-Finnish (FIN) AF: 0.388 AC: 66 AN: 170

Middle Eastern (MID) AF: 0.375 AC: 3 AN: 8

European-Non Finnish (NFE) AF: 0.375 AC: 479 AN: 1276

Other (OTH) AF: 0.577 AC: 15 AN: 26

Alfa AF: 0.373 Hom.: 308

ExAC AF: 0.190 AC: 1615

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.018
DANN	Benign	0.93
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00020	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.3
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.11
Sift	Benign	0.72	T
Sift4G	Benign	0.87	T
Vest4		0.093
ClinPred		0.0028	T
gMVP		0.000014
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV62127965;