NM_018406.7:c.12971G>A

Variant names:

• chr3-195774278-C-T
• rs2259292
• NM_018406.7:c.12971G>A

Variant summary

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

The NM_018406.7(MUC4):​c.12971G>A​(p.Gly4324Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,580,482 control chromosomes in the GnomAD database, including 261,628 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 0.58 (25712 hom., cov: 33)
  • Exomes 𝑓: 0.57 (235916 hom.)
• Consequence: MUC4 NM_018406.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 37 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=5.7244365E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC4	NM_018406.7	MANE Select	c.12971G>A	p.Gly4324Asp	missense	Exon 4 of 25	NP_060876.5
	MUC4	NM_004532.6		c.263G>A	p.Gly88Asp	missense	Exon 3 of 24	NP_004523.3
	MUC4	NM_138297.5		c.110G>A	p.Gly37Asp	missense	Exon 2 of 23	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.12971G>A	p.Gly4324Asp	missense	Exon 4 of 25	ENSP00000417498.3	Q99102-1
	MUC4	ENST00000346145.8	TSL:1	c.263G>A	p.Gly88Asp	missense	Exon 3 of 24	ENSP00000304207.6	Q99102-13
	MUC4	ENST00000349607.8	TSL:1	c.110G>A	p.Gly37Asp	missense	Exon 2 of 23	ENSP00000338109.4	Q99102-12

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87836 AN: 151932 Hom.: 25686 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.588

GnomAD2 exomes AF: 0.588 AC: 129333 AN: 220020 AF XY: 0.585

Gnomad AFR exome AF: 0.574

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.674

Gnomad EAS exome AF: 0.747

Gnomad FIN exome AF: 0.622

Gnomad NFE exome AF: 0.590

Gnomad OTH exome AF: 0.591

GnomAD4 exome AF: 0.573 AC: 817814 AN: 1428432 Hom.: 235916 Cov.: 55 AF XY: 0.571 AC XY: 404878 AN XY: 709074

African (AFR) AF: 0.575 AC: 18197 AN: 31632

American (AMR) AF: 0.509 AC: 20038 AN: 39386

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 16137 AN: 24172

East Asian (EAS) AF: 0.729 AC: 27826 AN: 38172

South Asian (SAS) AF: 0.501 AC: 40963 AN: 81706

European-Finnish (FIN) AF: 0.608 AC: 31552 AN: 51856

Middle Eastern (MID) AF: 0.544 AC: 3000 AN: 5510

European-Non Finnish (NFE) AF: 0.570 AC: 625803 AN: 1097094

Other (OTH) AF: 0.582 AC: 34298 AN: 58904

GnomAD4 genome AF: 0.578 AC: 87904 AN: 152050 Hom.: 25712 Cov.: 33 AF XY: 0.577 AC XY: 42861 AN XY: 74336

African (AFR) AF: 0.573 AC: 23746 AN: 41476

American (AMR) AF: 0.539 AC: 8230 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2285 AN: 3468

East Asian (EAS) AF: 0.741 AC: 3813 AN: 5148

South Asian (SAS) AF: 0.524 AC: 2527 AN: 4822

European-Finnish (FIN) AF: 0.618 AC: 6547 AN: 10592

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38767 AN: 67942

Other (OTH) AF: 0.592 AC: 1251 AN: 2114

Alfa AF: 0.581 Hom.: 88377

Bravo AF: 0.570

TwinsUK AF: 0.561 AC: 2079

ALSPAC AF: 0.563 AC: 2169

ESP6500AA AF: 0.586 AC: 2582

ESP6500EA AF: 0.580 AC: 4991

ExAC AF: 0.576 AC: 69768

Asia WGS AF: 0.681 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.60
DANN	Benign	0.82
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.055	T
MetaRNN	Benign	0.0000057	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.15
Sift	Benign	0.67	T
Sift4G	Benign	0.47	T
Polyphen		0.0060	B
Vest4		0.21
ClinPred		0.0063	T
GERP RS		-2.1
gMVP		0.24
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: rs2259292; hg19: chr3-195501149; COSMIC: COSV57772741; COSMIC: COSV57772741;