rs199812923

Variant names:

• chr3-195783357-C-A
• rs199812923
• NM_018406.7:c.8223G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-195783357-C-A
• chr3-195783357-C-G
• chr3-195783357-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018406.7(MUC4):​c.8223G>T​(p.Glu2741Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.020 (50 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 10 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008604169).
• BS2: High Homozygotes in GnomAdExome4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC4	NM_018406.7	c.8223G>T	p.Glu2741Asp	missense_variant	Exon 2 of 25	ENST00000463781.8	NP_060876.5
MUC4	NM_004532.6	c.83-4902G>T		intron_variant	Intron 1 of 23		NP_004523.3
MUC4	NM_138297.5	c.83-9052G>T		intron_variant	Intron 1 of 22		NP_612154.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC4	ENST00000463781.8	c.8223G>T	p.Glu2741Asp	missense_variant	Exon 2 of 25	5	NM_018406.7	ENSP00000417498.3

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 29 AN: 9372 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00314

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00103 AC: 47 AN: 45466 AF XY: 0.00114

Gnomad AFR exome AF: 0.000454

Gnomad AMR exome AF: 0.00134

Gnomad ASJ exome AF: 0.000987

Gnomad EAS exome AF: 0.000833

Gnomad FIN exome AF: 0.000260

Gnomad NFE exome AF: 0.00138

Gnomad OTH exome AF: 0.00267

GnomAD4 exome AF: 0.0196 AC: 6361 AN: 323824 Hom.: 50 Cov.: 8 AF XY: 0.0198 AC XY: 3189 AN XY: 160996

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

African (AFR) AF: 0.0408 AC: 483 AN: 11826

American (AMR) AF: 0.0259 AC: 201 AN: 7748

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 129 AN: 5796

East Asian (EAS) AF: 0.00427 AC: 40 AN: 9372

South Asian (SAS) AF: 0.0106 AC: 219 AN: 20708

European-Finnish (FIN) AF: 0.00604 AC: 60 AN: 9942

Middle Eastern (MID) AF: 0.0183 AC: 15 AN: 820

European-Non Finnish (NFE) AF: 0.0204 AC: 4972 AN: 243804

Other (OTH) AF: 0.0175 AC: 242 AN: 13808

⚠️ 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 AF: 0.00330 AC: 31 AN: 9384 Hom.: 0 Cov.: 0 AF XY: 0.00428 AC XY: 19 AN XY: 4436

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

African (AFR) AF: 0.00808 AC: 23 AN: 2848

American (AMR) AF: 0.00139 AC: 1 AN: 722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 338

East Asian (EAS) AF: 0.00316 AC: 1 AN: 316

South Asian (SAS) AF: 0.00 AC: 0 AN: 134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 16

European-Non Finnish (NFE) AF: 0.00140 AC: 6 AN: 4292

Other (OTH) AF: 0.00 AC: 0 AN: 132

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000104 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.18
DANN	Benign	0.31
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.00047	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.00044	T
MetaRNN	Benign	0.0086	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.0060
Sift	Benign	1.0	T;T
Sift4G	Benign	0.54	T;T
Vest4		0.047
MVP		0.014
ClinPred		0.0038	T
GERP RS		-1.4
gMVP		0.000053
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: rs199812923; hg19: chr3-195510228;