ENST00000394888.8:c.-132_-131dupGG

Variant names:

• chr11-61429988-G-GCC
• rs34378918
• ENST00000394888.8:c.-132_-131dupGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000394888.8(CPSF7):​c.-132_-131dupGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: CPSF7 ENST00000394888.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 0 publications found

Genes affected

CPSF7 (HGNC:30098): (cleavage and polyadenylation specific factor 7) Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes. [provided by RefSeq, Oct 2016]

ENSG00000256591 (HGNC:):

SDHAF2 (HGNC:26034): (succinate dehydrogenase complex assembly factor 2) This gene encodes a mitochondrial assembly factor needed for the flavination of a succinate dehydrogenase complex subunit (SDHA), which is required for activity of the succinate dehydrogenase complex. Mutations in this gene are associated with paraganglioma. [provided by RefSeq, May 2022]

SDHAF2 Gene-Disease associations (from GenCC):

• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• pheochromocytoma/paraganglioma syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394888.8. 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
	CPSF7	NM_001142565.3	MANE Select	c.-131_-130insGG		upstream_gene	N/A	NP_001136037.1	Q8N684-2
	SDHAF2	NM_017841.4	MANE Select	c.-159_-158insCC		upstream_gene	N/A	NP_060311.1	Q9NX18
	CPSF7	NM_024811.4		c.-159_-158insGG		upstream_gene	N/A	NP_079087.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPSF7	ENST00000394888.8	TSL:2	c.-132_-131dupGG		5_prime_UTR	Exon 1 of 10	ENSP00000378352.4	Q8N684-1
	CPSF7	ENST00000859449.1		c.-132_-131dupGG		5_prime_UTR	Exon 1 of 9	ENSP00000529508.1
	CPSF7	ENST00000859445.1		c.-56+56_-56+57dupGG		intron	N/A	ENSP00000529504.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000382 AC: 4 AN: 1047226 Hom.: 0 Cov.: 0 AF XY: 0.00000382 AC XY: 2 AN XY: 524232

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23510

American (AMR) AF: 0.00 AC: 0 AN: 28536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19196

East Asian (EAS) AF: 0.00 AC: 0 AN: 33016

South Asian (SAS) AF: 0.00 AC: 0 AN: 63910

European-Finnish (FIN) AF: 0.0000278 AC: 1 AN: 36012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3326

European-Non Finnish (NFE) AF: 0.00000378 AC: 3 AN: 793616

Other (OTH) AF: 0.00 AC: 0 AN: 46104

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000300874), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs34378918; hg19: chr11-61197460;