3-8736942-A-T

Position:

• chr3-8736942-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000343849.3(CAV3):​c.114+2952A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,254 control chromosomes in the GnomAD database, including 1,031 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 0.11 (1031 hom., cov: 33)
• Consequence: CAV3 ENST00000343849.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV3	NM_033337.3	c.114+2952A>T		intron_variant		ENST00000343849.3	NP_203123.1
CAV3	NM_001234.5	c.114+2952A>T		intron_variant			NP_001225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000343849.3	c.114+2952A>T		intron_variant		1	NM_033337.3	ENSP00000341940	P1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16645 AN: 152136 Hom.: 1027 Cov.: 33

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.109 AC: 16660 AN: 152254 Hom.: 1031 Cov.: 33 AF XY: 0.106 AC XY: 7867 AN XY: 74440

Gnomad4 AFR AF: 0.0821

Gnomad4 AMR AF: 0.0914

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0659 Hom.: 75

Bravo AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.47

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: rs13061909; hg19: chr3-8778628;