rs237870

Variant names:

• chr3-8737380-T-C
• rs237870
• NM_033337.3:c.114+3390T>C

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+3390T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,994 control chromosomes in the GnomAD database, including 13,793 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 0.39 (13793 hom., cov: 32)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV3	NM_033337.3	MANE Select	c.114+3390T>C		intron	N/A	NP_203123.1
	CAV3	NM_001234.5		c.114+3390T>C		intron	N/A	NP_001225.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAV3	ENST00000343849.3	TSL:1 MANE Select	c.114+3390T>C		intron	N/A	ENSP00000341940.2
	CAV3	ENST00000397368.2	TSL:1	c.114+3390T>C		intron	N/A	ENSP00000380525.2
	SSUH2	ENST00000478513.1	TSL:1	n.335+5079A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59807 AN: 151876 Hom.: 13764 Cov.: 32

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.394 AC: 59880 AN: 151994 Hom.: 13793 Cov.: 32 AF XY: 0.389 AC XY: 28885 AN XY: 74284

African (AFR) AF: 0.661 AC: 27367 AN: 41430

American (AMR) AF: 0.326 AC: 4980 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3470

East Asian (EAS) AF: 0.190 AC: 980 AN: 5162

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4812

European-Finnish (FIN) AF: 0.275 AC: 2901 AN: 10562

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20312 AN: 67954

Other (OTH) AF: 0.365 AC: 769 AN: 2108

Alfa AF: 0.321 Hom.: 34235

Bravo AF: 0.407

Asia WGS AF: 0.269 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.48
PhyloP100		-0.67
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: rs237870; hg19: chr3-8779066;