chr3-195787857-T-G

Variant names:

• chr3-195787857-T-G
• rs530253873
• NM_018406.7:c.3723A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_018406.7(MUC4):​c.3723A>C​(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A1241A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 1)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MUC4 NM_018406.7 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	NM_018406.7	MANE Select	c.3723A>C	p.Ala1241Ala	synonymous	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-9402A>C		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-13552A>C		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.3723A>C	p.Ala1241Ala	synonymous	Exon 2 of 25	ENSP00000417498.3
	MUC4	ENST00000346145.8	TSL:1	c.83-9402A>C		intron	N/A	ENSP00000304207.6
	MUC4	ENST00000349607.8	TSL:1	c.83-13552A>C		intron	N/A	ENSP00000338109.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 5648 Hom.: 0 Cov.: 1

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: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 429586 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 225572

African (AFR) AF: 0.00 AC: 0 AN: 9882

American (AMR) AF: 0.00 AC: 0 AN: 20356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11824

East Asian (EAS) AF: 0.00 AC: 0 AN: 27812

South Asian (SAS) AF: 0.00 AC: 0 AN: 44974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 262970

Other (OTH) AF: 0.00 AC: 0 AN: 23296

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 5648 Hom.: 0 Cov.: 1 AF XY: 0.00 AC XY: 0 AN XY: 2632

African (AFR) AF: 0.00 AC: 0 AN: 454

American (AMR) AF: 0.00 AC: 0 AN: 900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 146

East Asian (EAS) AF: 0.00 AC: 0 AN: 188

South Asian (SAS) AF: 0.00 AC: 0 AN: 266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 36

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3196

Other (OTH) AF: 0.00 AC: 0 AN: 76

Alfa AF: 0.00 Hom.: 14

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.35
PhyloP100		0.32

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: rs530253873; hg19: chr3-195514728;