10-126505010-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001350921.2(C10orf90):c.481A>C(p.Arg161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,614,246 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00091 (7 hom.)
• Consequence: C10orf90 NM_001350921.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.523

Genes affected

C10orf90 (HGNC:26563): (chromosome 10 open reading frame 90) Predicted to enable histone deacetylase binding activity; microtubule binding activity; and ubiquitin protein ligase activity. Predicted to be involved in several processes, including protein stabilization; regulation of cell cycle process; and response to ionizing radiation. Located in several cellular components, including cytoskeleton; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-126505010-T-G is Benign according to our data. Variant chr10-126505010-T-G is described in ClinVar as [Benign]. Clinvar id is 780918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.523 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00688 (1048/152366) while in subpopulation AFR AF= 0.0235 (978/41590). AF 95% confidence interval is 0.0223. There are 11 homozygotes in gnomad4. There are 513 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C10orf90	NM_001350921.2	c.481A>C	p.Arg161=	synonymous_variant	4/10	ENST00000488181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C10orf90	ENST00000488181.3	c.481A>C	p.Arg161=	synonymous_variant	4/10	2	NM_001350921.2	P2

Frequencies

GnomAD3 genomes AF: 0.00685 AC: 1043 AN: 152248 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00207 AC: 516 AN: 249376 Hom.: 5 AF XY: 0.00147 AC XY: 199 AN XY: 134944

Gnomad AFR exome AF: 0.0245

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000224

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000908 AC: 1327 AN: 1461880 Hom.: 7 Cov.: 33 AF XY: 0.000800 AC XY: 582 AN XY: 727244

Gnomad4 AFR exome AF: 0.0258

Gnomad4 AMR exome AF: 0.00188

Gnomad4 ASJ exome AF: 0.00279

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000156

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.00688 AC: 1048 AN: 152366 Hom.: 11 Cov.: 33 AF XY: 0.00688 AC XY: 513 AN XY: 74514

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000170 Hom.: 3

Bravo AF: 0.00821

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	1.5
Dann	Benign	0.63

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: rs75904847; hg19: chr10-128193579;