rs1218988871

Variant names:

• chr8-68331069-C-A
• rs1218988871
• NM_052958.4:c.57C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-68331069-C-A
• chr8-68331069-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052958.4(C8orf34):​c.57C>A​(p.Phe19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000769 in 1,300,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: C8orf34 NM_052958.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 0 publications found

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]

C8orf34-AS1 (HGNC:27840): (C8orf34 antisense RNA 1)

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0764533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052958.4. 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
	C8orf34	NM_052958.4	MANE Select	c.57C>A	p.Phe19Leu	missense	Exon 1 of 14	NP_443190.2	Q49A92-6
	C8orf34	NM_001349476.1		c.57C>A	p.Phe19Leu	missense	Exon 1 of 14	NP_001336405.1
	C8orf34	NM_001349477.1		c.57C>A	p.Phe19Leu	missense	Exon 1 of 13	NP_001336406.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8orf34	ENST00000518698.6	TSL:2 MANE Select	c.57C>A	p.Phe19Leu	missense	Exon 1 of 14	ENSP00000427820.1	Q49A92-6
	C8orf34-AS1	ENST00000512294.7	TSL:1	n.203+238G>T		intron	N/A
	C8orf34	ENST00000924297.1		c.57C>A	p.Phe19Leu	missense	Exon 1 of 15	ENSP00000594356.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.69e-7 AC: 1 AN: 1300198 Hom.: 0 Cov.: 31 AF XY: 0.00000156 AC XY: 1 AN XY: 641344

African (AFR) AF: 0.00 AC: 0 AN: 24258

American (AMR) AF: 0.00 AC: 0 AN: 23988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22776

East Asian (EAS) AF: 0.00 AC: 0 AN: 31192

South Asian (SAS) AF: 0.00 AC: 0 AN: 71068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3994

European-Non Finnish (NFE) AF: 9.64e-7 AC: 1 AN: 1036870

Other (OTH) AF: 0.00 AC: 0 AN: 53866

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	13
DANN	Uncertain	0.99
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.053
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.019
Sift	Benign	0.54	T
Sift4G	Benign	0.37	T
Vest4		0.020
MutPred		0.10		Gain of MoRF binding (P = 0.1078)
MVP		0.31
MPC		0.19
ClinPred		0.45	T
GERP RS		1.1
PromoterAI		-0.21	Neutral
Varity_R		0.037
gMVP		0.086
Mutation Taster		=97/3	polymorphism

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: rs1218988871; hg19: chr8-69243304;