chr3-8734016-G-A

Variant names:

• chr3-8734016-G-A
• rs11922879
• NM_033337.3:c.114+26G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001234.5(CAV3):​c.114+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 1,382,150 control chromosomes in the GnomAD database, including 2,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (665 hom., cov: 30)
  • Exomes 𝑓: 0.051 (1975 hom.)
• Consequence: CAV3 NM_001234.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.842
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-8734016-G-A is Benign according to our data. Variant chr3-8734016-G-A is described in ClinVar as Benign. ClinVar VariationId is 31723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001234.5. 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+26G>A		intron	N/A	NP_203123.1
	CAV3	NM_001234.5		c.114+26G>A		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+26G>A		intron	N/A	ENSP00000341940.2
	CAV3	ENST00000397368.2	TSL:1	c.114+26G>A		intron	N/A	ENSP00000380525.2
	SSUH2	ENST00000478513.1	TSL:1	n.335+8443C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0781 AC: 11861 AN: 151850 Hom.: 663 Cov.: 30

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.00464

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0680

GnomAD2 exomes AF: 0.0498 AC: 12196 AN: 244726 AF XY: 0.0481

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.0226

Gnomad ASJ exome AF: 0.0465

Gnomad EAS exome AF: 0.00293

Gnomad FIN exome AF: 0.0719

Gnomad NFE exome AF: 0.0501

Gnomad OTH exome AF: 0.0436

GnomAD4 exome AF: 0.0509 AC: 62608 AN: 1230184 Hom.: 1975 Cov.: 17 AF XY: 0.0502 AC XY: 31274 AN XY: 623340

African (AFR) AF: 0.160 AC: 4535 AN: 28338

American (AMR) AF: 0.0253 AC: 1115 AN: 44098

Ashkenazi Jewish (ASJ) AF: 0.0477 AC: 1171 AN: 24550

East Asian (EAS) AF: 0.00124 AC: 48 AN: 38570

South Asian (SAS) AF: 0.0399 AC: 3256 AN: 81668

European-Finnish (FIN) AF: 0.0726 AC: 3833 AN: 52826

Middle Eastern (MID) AF: 0.0377 AC: 201 AN: 5328

European-Non Finnish (NFE) AF: 0.0503 AC: 45354 AN: 902020

Other (OTH) AF: 0.0586 AC: 3095 AN: 52786

GnomAD4 genome AF: 0.0781 AC: 11874 AN: 151966 Hom.: 665 Cov.: 30 AF XY: 0.0774 AC XY: 5747 AN XY: 74284

African (AFR) AF: 0.155 AC: 6425 AN: 41420

American (AMR) AF: 0.0448 AC: 685 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3470

East Asian (EAS) AF: 0.00465 AC: 24 AN: 5158

South Asian (SAS) AF: 0.0422 AC: 202 AN: 4788

European-Finnish (FIN) AF: 0.0759 AC: 803 AN: 10584

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0503 AC: 3418 AN: 67944

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

Alfa AF: 0.0596 Hom.: 507

Bravo AF: 0.0770

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.31
DANN	Benign	0.86
PhyloP100		-0.84
PromoterAI		0.0056	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11922879; hg19: chr3-8775702;