rs530253873

Variant names:

• chr3-195787857-T-A
• rs530253873
• NM_018406.7:c.3723A>T
• MUC4 p.Ala1241Ala

Your query was ambiguous. Multiple possible variants found:

• chr3-195787857-T-A
• chr3-195787857-T-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_018406.7(MUC4):​c.3723A>T​(p.Ala1241Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (109 hom., cov: 1)
  • Exomes 𝑓: 0.45 (51911 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.319
• Publications: 2 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-195787857-T-A is Benign according to our data. Variant chr3-195787857-T-A is described in ClinVar as Benign. ClinVar VariationId is 403123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.319 with no splicing effect.

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.3723A>T	p.Ala1241Ala	synonymous	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-9402A>T		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-13552A>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.3723A>T	p.Ala1241Ala	synonymous	Exon 2 of 25	ENSP00000417498.3	Q99102-1
	MUC4	ENST00000346145.8	TSL:1	c.83-9402A>T		intron	N/A	ENSP00000304207.6	Q99102-13
	MUC4	ENST00000349607.8	TSL:1	c.83-13552A>T		intron	N/A	ENSP00000338109.4	Q99102-12

Frequencies

GnomAD3 genomes AF: 0.116 AC: 650 AN: 5590 Hom.: 109 Cov.: 1

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0556

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.171

GnomAD2 exomes AF: 0.362 AC: 16147 AN: 44546 AF XY: 0.362

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.258

Gnomad ASJ exome AF: 0.452

Gnomad EAS exome AF: 0.544

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.382

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.450 AC: 189356 AN: 420360 Hom.: 51911 Cov.: 4 AF XY: 0.449 AC XY: 99220 AN XY: 220772

African (AFR) AF: 0.423 AC: 4168 AN: 9842

American (AMR) AF: 0.323 AC: 6369 AN: 19744

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 6497 AN: 11588

East Asian (EAS) AF: 0.663 AC: 17760 AN: 26770

South Asian (SAS) AF: 0.382 AC: 16717 AN: 43728

European-Finnish (FIN) AF: 0.511 AC: 13269 AN: 25974

Middle Eastern (MID) AF: 0.365 AC: 613 AN: 1680

European-Non Finnish (NFE) AF: 0.439 AC: 113240 AN: 258184

Other (OTH) AF: 0.469 AC: 10723 AN: 22850

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.116 AC: 650 AN: 5586 Hom.: 109 Cov.: 1 AF XY: 0.117 AC XY: 304 AN XY: 2602

African (AFR) AF: 0.122 AC: 55 AN: 452

American (AMR) AF: 0.107 AC: 95 AN: 886

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 26 AN: 142

East Asian (EAS) AF: 0.197 AC: 35 AN: 178

South Asian (SAS) AF: 0.0644 AC: 17 AN: 264

European-Finnish (FIN) AF: 0.144 AC: 50 AN: 348

Middle Eastern (MID) AF: 0.0385 AC: 1 AN: 26

European-Non Finnish (NFE) AF: 0.111 AC: 354 AN: 3182

Other (OTH) AF: 0.171 AC: 13 AN: 76

Alfa AF: 0.0683 Hom.: 14

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
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.37
PhyloP100		0.32
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs530253873; hg19: chr3-195514728; COSMIC: COSV62129552;