chr3-195790007-T-C

Position:

• chr3-195790007-T-C

Variant summary

Our verdict is Benign. Variant got -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. 12/16 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC4	NM_018406.7	c.1573A>G	p.Thr525Ala	missense_variant	2/25	ENST00000463781.8
MUC4	NM_004532.6	c.83-11552A>G		intron_variant
MUC4	NM_138297.5	c.83-15702A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC4	ENST00000463781.8	c.1573A>G	p.Thr525Ala	missense_variant	2/25	5	NM_018406.7	A2

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

GnomAD3 exomes AF: 0.775 AC: 193199 AN: 249202 Hom.: 75697 AF XY: 0.776 AC XY: 104849 AN XY: 135178

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 SAS exome AF: 0.665

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

Gnomad4 AFR exome AF: 0.815

Gnomad4 AMR exome AF: 0.637

Gnomad4 ASJ exome AF: 0.848

Gnomad4 EAS exome AF: 0.813

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.792

Gnomad4 NFE exome AF: 0.823

Gnomad4 OTH exome AF: 0.811

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

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.824

Alfa AF: 0.821 Hom.: 126873

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 v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaRNN	Benign	0.0000039	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.10	N;N
REVEL	Benign	0.014
Sift	Benign	1.0	T;T
Sift4G	Benign	0.49	T;T
Vest4		0.060
ClinPred		0.0072	T
GERP RS		-2.8
gMVP		0.019

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

Publications

LitVar

Other links and lift over

dbSNP: rs2177336; hg19: chr3-195516878;