NM_052958.4:c.1328-3T>G

Variant names:

• chr8-68721358-T-G
• NM_052958.4:c.1328-3T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052958.4(C8orf34):​c.1328-3T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C8orf34 NM_052958.4 splice_region, intron
• Scores: Splicing: ADA: 0.1798
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8orf34	NM_052958.4	c.1328-3T>G		splice_region_variant, intron_variant	Intron 9 of 13	ENST00000518698.6	NP_443190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8orf34	ENST00000518698.6	c.1328-3T>G		splice_region_variant, intron_variant	Intron 9 of 13	2	NM_052958.4	ENSP00000427820.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442032 Hom.: 0 Cov.: 28 AF XY: 0.00000139 AC XY: 1 AN XY: 717974

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.18
dbscSNV1_RF	Benign	0.58
SpliceAI score (max)		0.79		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 1
DS_AL_spliceai		0.79		Position offset: 3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-69633593;