3-8741758-C-T

Position:

• chr3-8741758-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_033337.3(CAV3):​c.115-3768C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 152,152 control chromosomes in the GnomAD database, including 62 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 0.025 (62 hom., cov: 31)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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:):

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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0252 (3840/152152) while in subpopulation NFE AF= 0.0319 (2169/68006). AF 95% confidence interval is 0.0308. There are 62 homozygotes in gnomad4. There are 1895 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3840 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV3	NM_033337.3	c.115-3768C>T		intron_variant		ENST00000343849.3	NP_203123.1
CAV3	NM_001234.5	c.115-3768C>T		intron_variant			NP_001225.1
OXTR	XR_007095681.1	n.2729G>A		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000343849.3	c.115-3768C>T		intron_variant		1	NM_033337.3	ENSP00000341940.2

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3839 AN: 152036 Hom.: 62 Cov.: 31

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0205

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00894

Gnomad FIN AF: 0.0359

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0254

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

GnomAD4 genome AF: 0.0252 AC: 3840 AN: 152152 Hom.: 62 Cov.: 31 AF XY: 0.0255 AC XY: 1895 AN XY: 74376

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00916

Gnomad4 FIN AF: 0.0359

Gnomad4 NFE AF: 0.0319

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.00709 Hom.: 2

Bravo AF: 0.0243

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.61

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: rs237879; hg19: chr3-8783444;