10-126425986-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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, single submitter B:1
• Conservation: PhyloP100: -1.12

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 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_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 445 AN: 152220 Hom.: 3 Cov.: 33

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.: 1 AF XY: 0.000574 AC XY: 78 AN XY: 135840

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.: 0 Cov.: 31 AF XY: 0.000268 AC XY: 195 AN XY: 727188

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.: 3 Cov.: 33 AF XY: 0.00271 AC XY: 202 AN XY: 74498

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.: 0

Bravo AF: 0.00339

ESP6500AA AF: 0.00976 AC: 43

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00110 AC: 134

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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

Aug 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	1.5
Dann	Benign	0.77
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0027	T
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

Other links and lift over

dbSNP: rs182354709; hg19: chr10-128114555;