chr7-100959000-T-A

Variant names:

• chr7-100959000-T-A
• rs760549664
• NM_005960.2:c.7221T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005960.2(MUC3A):​c.7221T>A​(p.Pro2407Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. P2407P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MUC3A NM_005960.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 0 publications found

Genes affected

MUC3A (HGNC:7513): (mucin 3A, cell surface associated) The mucin genes encode epithelial glycoproteins, some of which are secreted and some membrane bound. Each of the genes contains at least one large domain of tandemly repeated sequence that encodes the peptide sequence rich in serine and/or threonine residues, which carries most of the O-linked glycosylation (Gendler and Spicer, 1995 [PubMed 7778880]).[supplied by OMIM, Aug 2008]

LOC105375431 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-2.94 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005960.2. 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
	MUC3A	NM_005960.2	MANE Select	c.7221T>A	p.Pro2407Pro	synonymous	Exon 2 of 12	NP_005951.1	Q02505-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MUC3A	ENST00000379458.9	TSL:5 MANE Select	c.7221T>A	p.Pro2407Pro	synonymous	Exon 2 of 12	ENSP00000368771.5	Q02505-1
	MUC3A	ENST00000483366.5	TSL:5	c.7221T>A	p.Pro2407Pro	synonymous	Exon 2 of 11	ENSP00000483541.1	Q02505-5
	MUC3A	ENST00000868577.1		c.62-1752T>A		intron	N/A	ENSP00000538636.1

Frequencies

GnomAD3 genomes AF: 0.000676 AC: 1 AN: 1480 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00269

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 Cov.: 100

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000676 AC: 1 AN: 1480 Hom.: 0 Cov.: 0 AF XY: 0.00140 AC XY: 1 AN XY: 716

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

African (AFR) AF: 0.00269 AC: 1 AN: 372

American (AMR) AF: 0.00 AC: 0 AN: 166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22

East Asian (EAS) AF: 0.00 AC: 0 AN: 64

South Asian (SAS) AF: 0.00 AC: 0 AN: 54

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 628

Other (OTH) AF: 0.00 AC: 0 AN: 22

⚠️ 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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.0
DANN	Benign	0.43
PhyloP100		-2.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs760549664; hg19: chr7-100551129;