3-8741758-C-T

Variant names:

• chr3-8741758-C-T
• rs237879
• NM_033337.3:c.115-3768C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 62 AD,AR gene

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.115-3768C>T		intron	N/A	NP_203123.1	P56539
	CAV3	NM_001234.5		c.115-3768C>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.115-3768C>T		intron	N/A	ENSP00000341940.2	P56539
	CAV3	ENST00000397368.2	TSL:1	c.115-3768C>T		intron	N/A	ENSP00000380525.2	P56539
	SSUH2	ENST00000478513.1	TSL:1	n.335+701G>A		intron	N/A

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

African (AFR) AF: 0.0201 AC: 834 AN: 41506

American (AMR) AF: 0.0205 AC: 313 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.00916 AC: 44 AN: 4804

European-Finnish (FIN) AF: 0.0359 AC: 381 AN: 10602

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2169 AN: 68006

Other (OTH) AF: 0.0251 AC: 53 AN: 2112

Alfa AF: 0.0271 Hom.: 50

Bravo AF: 0.0243

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.61
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism

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: rs237879; hg19: chr3-8783444;