rs979455

Positions:

• chr5-151215241-T-C

Variant summary

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

The NM_015621.3(CCDC69):​c.48+8682A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,024 control chromosomes in the GnomAD database, including 7,182 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 0.30 (7182 hom., cov: 32)
• Consequence: CCDC69 NM_015621.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

Genes affected

CCDC69 (HGNC:24487): (coiled-coil domain containing 69) Predicted to enable microtubule binding activity. Involved in spindle midzone assembly. Located in spindle midzone. [provided by Alliance of Genome Resources, Apr 2022]

CCDC69 (HGNC:):

GM2A (HGNC:4367): (ganglioside GM2 activator) This gene encodes a small glycolipid transport protein which acts as a substrate specific co-factor for the lysosomal enzyme beta-hexosaminidase A. Beta-hexosaminidase A, together with GM2 ganglioside activator, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Mutations in this gene result in GM2-gangliosidosis type AB or the AB variant of Tay-Sachs disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC69	NM_015621.3	c.48+8682A>G		intron_variant		ENST00000355417.7	NP_056436.2
LOC105378230	NR_160730.1	n.257+2352T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC69	ENST00000355417.7	c.48+8682A>G		intron_variant		1	NM_015621.3	ENSP00000347586.2
CCDC69	ENST00000521308.5	n.171+8682A>G		intron_variant		1
GM2A	ENST00000523466.5	c.126+2352T>C		intron_variant		3		ENSP00000429100.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46117 AN: 151908 Hom.: 7171 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.304 AC: 46161 AN: 152024 Hom.: 7182 Cov.: 32 AF XY: 0.300 AC XY: 22286 AN XY: 74336

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.325

Gnomad4 OTH AF: 0.297

Alfa AF: 0.318 Hom.: 7685

Bravo AF: 0.303

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs979455; hg19: chr5-150594802; COSMIC: COSV62599371; COSMIC: COSV62599371;