8-145054094-T-G

Position:

• chr8-145054094-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_023080.3(C8orf33):​c.627T>G​(p.Ser209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,200 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (20 hom.)
• Consequence: C8orf33 NM_023080.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.335

Genes affected

C8orf33 (HGNC:26104): (chromosome 8 open reading frame 33)

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-145054094-T-G is Benign according to our data. Variant chr8-145054094-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2659004.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.335 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C8orf33	NM_023080.3	c.627T>G	p.Ser209=	synonymous_variant	5/5	ENST00000331434.7	NP_075568.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C8orf33	ENST00000331434.7	c.627T>G	p.Ser209=	synonymous_variant	5/5	1	NM_023080.3	ENSP00000330361	P1

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 244 AN: 152202 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00194 AC: 489 AN: 251456 Hom.: 10 AF XY: 0.00174 AC XY: 237 AN XY: 135900

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.0368

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.000956 AC: 1397 AN: 1461880 Hom.: 20 Cov.: 30 AF XY: 0.000967 AC XY: 703 AN XY: 727246

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.0359

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000197

Gnomad4 OTH exome AF: 0.00252

GnomAD4 genome AF: 0.00160 AC: 244 AN: 152320 Hom.: 4 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74476

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00321 Hom.: 5

Bravo AF: 0.00182

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000593

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

Sep 01, 2022

C8orf33: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs150773218; hg19: chr8-146279480;