rs10506030

Variant names:

• chr12-28362948-A-T
• rs10506030
• NM_018318.5:c.654+433A>T

Variant summary

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

The NM_018318.5(CCDC91):​c.654+433A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 152,148 control chromosomes in the GnomAD database, including 123 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 0.032 (123 hom., cov: 33)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC91	NM_018318.5	c.654+433A>T		intron_variant	Intron 7 of 12	ENST00000536442.6	NP_060788.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC91	ENST00000536442.6	c.654+433A>T		intron_variant	Intron 7 of 12	5	NM_018318.5	ENSP00000445660.2

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4801 AN: 152030 Hom.: 123 Cov.: 33

Gnomad AFR AF: 0.00723

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0250

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.0142

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0325

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

GnomAD4 genome AF: 0.0315 AC: 4799 AN: 152148 Hom.: 123 Cov.: 33 AF XY: 0.0331 AC XY: 2459 AN XY: 74396

African (AFR) AF: 0.00721 AC: 299 AN: 41494

American (AMR) AF: 0.0249 AC: 380 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0935 AC: 324 AN: 3466

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5192

South Asian (SAS) AF: 0.127 AC: 614 AN: 4816

European-Finnish (FIN) AF: 0.0431 AC: 456 AN: 10590

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0367 AC: 2494 AN: 67988

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0322 Hom.: 13

Bravo AF: 0.0273

Asia WGS AF: 0.0550 AC: 186 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.35
PhyloP100		-0.41
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: rs10506030; hg19: chr12-28515881;