12-28253582-T-C

Variant names:

• chr12-28253582-T-C
• rs1979679
• NM_018318.5:c.-14-3620T>C

Variant summary

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

The NM_018318.5(CCDC91):​c.-14-3620T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,152 control chromosomes in the GnomAD database, including 5,265 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 0.25 (5265 hom., cov: 32)
• Consequence: CCDC91 NM_018318.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 14 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018318.5. 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
	CCDC91	NM_018318.5	MANE Select	c.-14-3620T>C		intron	N/A	NP_060788.3
	CCDC91	NM_001352078.2		c.-96-1999T>C		intron	N/A	NP_001339007.1
	CCDC91	NM_001352079.2		c.-96-1999T>C		intron	N/A	NP_001339008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC91	ENST00000536442.6	TSL:5 MANE Select	c.-14-3620T>C		intron	N/A	ENSP00000445660.2
	CCDC91	ENST00000545336.5	TSL:5	c.-96-1999T>C		intron	N/A	ENSP00000438040.1
	CCDC91	ENST00000539107.5	TSL:5	c.-14-3620T>C		intron	N/A	ENSP00000440513.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37902 AN: 152034 Hom.: 5258 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.249 AC: 37929 AN: 152152 Hom.: 5265 Cov.: 32 AF XY: 0.254 AC XY: 18890 AN XY: 74374

African (AFR) AF: 0.182 AC: 7557 AN: 41534

American (AMR) AF: 0.334 AC: 5100 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 998 AN: 3472

East Asian (EAS) AF: 0.566 AC: 2923 AN: 5164

South Asian (SAS) AF: 0.359 AC: 1730 AN: 4816

European-Finnish (FIN) AF: 0.239 AC: 2527 AN: 10582

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16292 AN: 67996

Other (OTH) AF: 0.261 AC: 552 AN: 2114

Alfa AF: 0.246 Hom.: 18596

Bravo AF: 0.250

Asia WGS AF: 0.400 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.52
PhyloP100		0.085
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: rs1979679; hg19: chr12-28406515;