8-68721358-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_052958.4(C8orf34):c.1328-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000928 in 1,594,094 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (16 hom.)
• Consequence: C8orf34 NM_052958.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002277
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0210

Genes affected

C8orf34 (HGNC:30905): (chromosome 8 open reading frame 34) This gene encodes a protein that is related to the cyclic AMP dependent protein kinase regulators. Naturally occurring mutations in this gene are associated with an increased risk for severe toxicities, such as diarrhea and neutropenia, in patients undergoing chemotherapeutic treatment. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 8-68721358-T-C is Benign according to our data. Variant chr8-68721358-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3024951.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C8orf34	NM_052958.4	c.1328-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000518698.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8orf34	ENST00000518698.6	c.1328-3T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_052958.4	P2

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 198 AN: 151960 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00168 AC: 412 AN: 244750 Hom.: 6 AF XY: 0.00198 AC XY: 262 AN XY: 132538

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000448

Gnomad ASJ exome AF: 0.0175

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00487

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000553

Gnomad OTH exome AF: 0.00283

GnomAD4 exome AF: 0.000889 AC: 1282 AN: 1442016 Hom.: 16 Cov.: 28 AF XY: 0.00107 AC XY: 767 AN XY: 717968

Gnomad4 AFR exome AF: 0.0000306

Gnomad4 AMR exome AF: 0.000435

Gnomad4 ASJ exome AF: 0.0166

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00501

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.00190

GnomAD4 genome AF: 0.00130 AC: 198 AN: 152078 Hom.: 6 Cov.: 32 AF XY: 0.00137 AC XY: 102 AN XY: 74340

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000983

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000427

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00166 Hom.: 0

Bravo AF: 0.00143

Asia WGS AF: 0.00464 AC: 16 AN: 3462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

C8orf34: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	6.4
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.018
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

Publications

LitVar

Other links and lift over

dbSNP: rs199668114; hg19: chr8-69633593;