chr3-46979533-A-T

Variant names:

• chr3-46979533-A-T
• rs13062516
• ENST00000605875.1:c.-108T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144716.6(CCDC12):​c.-73+2399T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC12 NM_144716.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 3 publications found

Genes affected

CCDC12 (HGNC:28332): (coiled-coil domain containing 12) Predicted to be part of U2-type spliceosomal complex and post-mRNA release spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

NBEAL2 (HGNC:31928): (neurobeachin like 2) The protein encoded by this gene contains a beige and Chediak-Higashi (BEACH) domain and multiple WD40 domains, and may play a role in megakaryocyte alpha-granule biogenesis. Mutations in this gene are a cause of gray platelet syndrome. [provided by RefSeq, Dec 2011]

NBEAL2 Gene-Disease associations (from GenCC):

• gray platelet syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144716.6. 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
	CCDC12	NM_144716.6		c.-73+2399T>A		intron	N/A	NP_653317.2	J3KR35
	NBEAL2	NM_015175.3	MANE Select	c.-329A>T		upstream_gene	N/A	NP_055990.1	Q6ZNJ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC12	ENST00000605875.1	TSL:5	c.-108T>A		5_prime_UTR	Exon 1 of 4	ENSP00000473887.2	S4R331
	CCDC12	ENST00000292314.6	TSL:5	c.-73+2399T>A		intron	N/A	ENSP00000292314.2	J3KR35
	CCDC12	ENST00000425441.5	TSL:5	c.-215+2399T>A		intron	N/A	ENSP00000416263.2	Q8WUD4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 42274 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 21550

African (AFR) AF: 0.00 AC: 0 AN: 1504

American (AMR) AF: 0.00 AC: 0 AN: 1116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1764

East Asian (EAS) AF: 0.00 AC: 0 AN: 3838

South Asian (SAS) AF: 0.00 AC: 0 AN: 450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 27298

Other (OTH) AF: 0.00 AC: 0 AN: 3026

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 4247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.67
PhyloP100		-0.40
PromoterAI		-0.0095	Neutral

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: rs13062516; hg19: chr3-47021023;