Variant 10-126425986-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001350921.2(C10orf90):c.2352+5T>C variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 1,614,092 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

C10orf90
NM_001350921.2 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.0001331

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.12

Variant links:

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]

C10orf90 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026852787).

BP6

Variant 10-126425986-A-G is Benign according to our data. Variant chr10-126425986-A-G is described in ClinVar as [Benign]. Clinvar id is 784173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
C10orf90	NM_001350921.2 linkuse as main transcript	c.2352+5T>C	splice_donor_5th_base_variant, intron_variant		ENST00000488181.3	NP_001337850.1
LOC728158	NR_148989.1 linkuse as main transcript	n.57A>G	non_coding_transcript_exon_variant	1/7
LOC112267914	XR_001747635.3 linkuse as main transcript	n.517+1086A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C10orf90	ENST00000488181.3 linkuse as main transcript	c.2352+5T>C		splice_donor_5th_base_variant, intron_variant		2	NM_001350921.2	ENSP00000474558	P2
	ENST00000656840.1 linkuse as main transcript	n.57A>G		non_coding_transcript_exon_variant	1/7

Frequencies

GnomAD3 genomes

AF:

0.00292

AC:

445

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000891

AC:

224

AN:

251360

Hom.:

AF XY:

0.000574

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000330

AC:

482

AN:

1461754

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

195

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.00292

AC:

445

AN:

152338

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

202

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000561

Hom.:

Bravo

AF:

0.00339

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00110

AC:

134

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 02, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.5

DANN

Benign

0.77

DEOGEN2

Benign

0.024

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0027

MutationTaster

Benign

1.0

N;N;N;N

Vest4

0.17

MVP

0.085

GERP RS

-6.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.040

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over