rs4686300

Variant names:

• chr3-8737062-C-T
• rs4686300
• NM_033337.3:c.114+3072C>T

Variant summary

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

The NM_033337.3(CAV3):​c.114+3072C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 152,100 control chromosomes in the GnomAD database, including 339 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.050 (339 hom., cov: 32)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510
• Publications: 2 publications found

Genes affected

CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]

SSUH2 (HGNC:24809): (ssu-2 homolog) Involved in odontogenesis. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SSUH2 Gene-Disease associations (from GenCC):

• dentin dysplasia type I

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033337.3. 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
	CAV3	NM_033337.3	MANE Select	c.114+3072C>T		intron	N/A	NP_203123.1	P56539
	CAV3	NM_001234.5		c.114+3072C>T		intron	N/A	NP_001225.1	P56539

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV3	ENST00000343849.3	TSL:1 MANE Select	c.114+3072C>T		intron	N/A	ENSP00000341940.2	P56539
	CAV3	ENST00000397368.2	TSL:1	c.114+3072C>T		intron	N/A	ENSP00000380525.2	P56539
	SSUH2	ENST00000478513.1	TSL:1	n.335+5397G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7550 AN: 151982 Hom.: 339 Cov.: 32

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0866

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0344

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0497 AC: 7557 AN: 152100 Hom.: 339 Cov.: 32 AF XY: 0.0542 AC XY: 4030 AN XY: 74354

African (AFR) AF: 0.0346 AC: 1436 AN: 41492

American (AMR) AF: 0.0562 AC: 859 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 123 AN: 3464

East Asian (EAS) AF: 0.226 AC: 1164 AN: 5144

South Asian (SAS) AF: 0.0869 AC: 419 AN: 4822

European-Finnish (FIN) AF: 0.0998 AC: 1056 AN: 10580

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0356 AC: 2418 AN: 67996

Other (OTH) AF: 0.0340 AC: 72 AN: 2116

Alfa AF: 0.0394 Hom.: 60

Bravo AF: 0.0476

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.37
PhyloP100		0.51
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: rs4686300; hg19: chr3-8778748;