10-126504015-G-A

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.1476C>T(p.His492=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,613,852 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (43 hom.)
• Consequence: C10orf90 NM_001350921.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.775

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=-0.91).
• BP6: Variant 10-126504015-G-A is Benign according to our data. Variant chr10-126504015-G-A is described in ClinVar as [Benign]. Clinvar id is 776553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.775 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1950/152258) while in subpopulation AFR AF= 0.0438 (1817/41528). AF 95% confidence interval is 0.0421. There are 30 homozygotes in gnomad4. There are 936 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C10orf90	NM_001350921.2	c.1476C>T	p.His492=	synonymous_variant	4/10	ENST00000488181.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C10orf90	ENST00000488181.3	c.1476C>T	p.His492=	synonymous_variant	4/10	2	NM_001350921.2	P2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1947 AN: 152140 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00391 AC: 982 AN: 251426 Hom.: 18 AF XY: 0.00279 AC XY: 379 AN XY: 135882

Gnomad AFR exome AF: 0.0464

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.000598

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00168 AC: 2460 AN: 1461594 Hom.: 43 Cov.: 31 AF XY: 0.00147 AC XY: 1067 AN XY: 727082

Gnomad4 AFR exome AF: 0.0467

Gnomad4 AMR exome AF: 0.00349

Gnomad4 ASJ exome AF: 0.00279

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000357

Gnomad4 OTH exome AF: 0.00359

GnomAD4 genome AF: 0.0128 AC: 1950 AN: 152258 Hom.: 30 Cov.: 32 AF XY: 0.0126 AC XY: 936 AN XY: 74454

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00639 Hom.: 5

Bravo AF: 0.0149

Asia WGS AF: 0.00606 AC: 22 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000533

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.68
Dann	Benign	0.49

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: rs73373045; hg19: chr10-128192584;