rs10506039

Variant names:

• chr12-28534398-A-G
• rs10506039
• NM_018318.5:c.1216-14665A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018318.5(CCDC91):​c.1216-14665A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 152,168 control chromosomes in the GnomAD database, including 1,485 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 0.080 (1485 hom., cov: 32)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 1 publications found

Genes affected

CCDC91 (HGNC:24855): (coiled-coil domain containing 91) Predicted to enable identical protein binding activity. Involved in Golgi to lysosome transport. Located in nucleoplasm and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

CCDC91 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• punctate palmoplantar keratoderma

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC91	NM_018318.5	c.1216-14665A>G		intron_variant	Intron 12 of 12	ENST00000536442.6	NP_060788.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC91	ENST00000536442.6	c.1216-14665A>G		intron_variant	Intron 12 of 12	5	NM_018318.5	ENSP00000445660.2

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12200 AN: 152050 Hom.: 1485 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0803 AC: 12223 AN: 152168 Hom.: 1485 Cov.: 32 AF XY: 0.0787 AC XY: 5858 AN XY: 74402

African (AFR) AF: 0.267 AC: 11051 AN: 41462

American (AMR) AF: 0.0383 AC: 585 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00414 AC: 20 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.00318 AC: 216 AN: 68020

Other (OTH) AF: 0.0644 AC: 136 AN: 2112

Alfa AF: 0.0581 Hom.: 124

Bravo AF: 0.0927

Asia WGS AF: 0.0200 AC: 70 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	0.49
DANN	Benign	0.87
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs10506039; hg19: chr12-28687331;