chr3-195790007-T-C

Variant names:

• chr3-195790007-T-C
• rs2177336
• NM_018406.7:c.1573A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018406.7(MUC4):​c.1573A>G​(p.Thr525Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 1,613,820 control chromosomes in the GnomAD database, including 527,007 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.80 (49028 hom., cov: 32)
  • Exomes 𝑓: 0.81 (477979 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 39 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=3.909326E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

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.1573A>G	p.Thr525Ala	missense	Exon 2 of 25	NP_060876.5
	MUC4	NM_004532.6		c.83-11552A>G		intron	N/A	NP_004523.3
	MUC4	NM_138297.5		c.83-15702A>G		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.1573A>G	p.Thr525Ala	missense	Exon 2 of 25	ENSP00000417498.3
	MUC4	ENST00000346145.8	TSL:1	c.83-11552A>G		intron	N/A	ENSP00000304207.6
	MUC4	ENST00000349607.8	TSL:1	c.83-15702A>G		intron	N/A	ENSP00000338109.4

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121789 AN: 152062 Hom.: 48991 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.822

GnomAD2 exomes AF: 0.775 AC: 193199 AN: 249202 AF XY: 0.776

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.633

Gnomad ASJ exome AF: 0.841

Gnomad EAS exome AF: 0.805

Gnomad FIN exome AF: 0.797

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.807 AC: 1179183 AN: 1461640 Hom.: 477979 Cov.: 85 AF XY: 0.803 AC XY: 584218 AN XY: 727102

African (AFR) AF: 0.815 AC: 27284 AN: 33478

American (AMR) AF: 0.637 AC: 28507 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 22170 AN: 26136

East Asian (EAS) AF: 0.813 AC: 32283 AN: 39700

South Asian (SAS) AF: 0.668 AC: 57631 AN: 86256

European-Finnish (FIN) AF: 0.792 AC: 42280 AN: 53402

Middle Eastern (MID) AF: 0.812 AC: 4681 AN: 5768

European-Non Finnish (NFE) AF: 0.823 AC: 915378 AN: 1111814

Other (OTH) AF: 0.811 AC: 48969 AN: 60368

GnomAD4 genome AF: 0.801 AC: 121874 AN: 152180 Hom.: 49028 Cov.: 32 AF XY: 0.796 AC XY: 59261 AN XY: 74404

African (AFR) AF: 0.815 AC: 33848 AN: 41510

American (AMR) AF: 0.711 AC: 10879 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2932 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4150 AN: 5174

South Asian (SAS) AF: 0.675 AC: 3255 AN: 4820

European-Finnish (FIN) AF: 0.802 AC: 8491 AN: 10592

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55644 AN: 68002

Other (OTH) AF: 0.824 AC: 1740 AN: 2112

Alfa AF: 0.818 Hom.: 172996

Bravo AF: 0.796

TwinsUK AF: 0.827 AC: 3066

ALSPAC AF: 0.824 AC: 3176

ESP6500AA AF: 0.823 AC: 3236

ESP6500EA AF: 0.824 AC: 6835

ExAC AF: 0.780 AC: 94301

Asia WGS AF: 0.807 AC: 2807 AN: 3478

EpiCase AF: 0.833

EpiControl AF: 0.838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.29
DANN	Benign	0.33
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0000039	T
MetaSVM	Benign	-0.96	T
PhyloP100		-2.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.014
Sift	Benign	1.0	T
Sift4G	Benign	0.49	T
Vest4		0.060
ClinPred		0.0072	T
GERP RS		-2.8
gMVP		0.019
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: rs2177336; hg19: chr3-195516878; COSMIC: COSV107442911;