13-24882861-C-T

Variant names:

• chr13-24882861-C-T
• rs1953900248
• NM_018451.5:c.*316G>A

Variant summary

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

The NM_018451.5(CPAP):​c.*316G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000477 in 209,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CPAP NM_018451.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -1.17
• Publications: 0 publications found

Genes affected

CPAP (HGNC:17272): (centromere protein J) This gene encodes a protein that belongs to the centromere protein family. During cell division, this protein plays a structural role in the maintenance of centrosome integrity and normal spindle morphology, and it is involved in microtubule disassembly at the centrosome. This protein can function as a transcriptional coactivator in the Stat5 signaling pathway, and also as a coactivator of NF-kappaB-mediated transcription, likely via its interaction with the coactivator p300/CREB-binding protein. Mutations in this gene are associated with primary autosomal recessive microcephaly, a disorder characterized by severely reduced brain size and cognitive disability. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2012]

RNF17 (HGNC:10060): (ring finger protein 17) This gene is similar to a mouse gene that encodes a testis-specific protein containing a RING finger domain. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, May 2010]

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=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018451.5. 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
	CPAP	NM_018451.5	MANE Select	c.*316G>A		3_prime_UTR	Exon 17 of 17	NP_060921.3
	CPAP	NR_047594.2		n.4617G>A		non_coding_transcript_exon	Exon 18 of 18
	CPAP	NR_047595.2		n.4415G>A		non_coding_transcript_exon	Exon 16 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAP	ENST00000381884.9	TSL:1 MANE Select	c.*316G>A		3_prime_UTR	Exon 17 of 17	ENSP00000371308.4	Q9HC77-1
	CPAP	ENST00000616936.4	TSL:1	n.*987G>A		non_coding_transcript_exon	Exon 16 of 16	ENSP00000477511.1	Q9HC77-2
	CPAP	ENST00000616936.4	TSL:1	n.*987G>A		3_prime_UTR	Exon 16 of 16	ENSP00000477511.1	Q9HC77-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000477 AC: 1 AN: 209470 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 114010

African (AFR) AF: 0.00 AC: 0 AN: 5772

American (AMR) AF: 0.00 AC: 0 AN: 8850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5520

East Asian (EAS) AF: 0.00 AC: 0 AN: 9382

South Asian (SAS) AF: 0.00 AC: 0 AN: 35356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9508

Middle Eastern (MID) AF: 0.00119 AC: 1 AN: 840

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 123400

Other (OTH) AF: 0.00 AC: 0 AN: 10842

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Microcephaly 6, primary, autosomal recessive (1)
-	1	-	Seckel syndrome 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.60
PhyloP100		-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1953900248; hg19: chr13-25456999;