chr10-126504556-C-T

Variant summary

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

The NM_001350921.2(C10orf90):​c.935G>A​(p.Gly312Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 1,614,214 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0037 ( 19 hom. )

Consequence

C10orf90
NM_001350921.2 missense

Scores

18

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.146
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0058040917).
BP6
Variant 10-126504556-C-T is Benign according to our data. Variant chr10-126504556-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 717882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C10orf90NM_001350921.2 linkuse as main transcriptc.935G>A p.Gly312Glu missense_variant 4/10 ENST00000488181.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C10orf90ENST00000488181.3 linkuse as main transcriptc.935G>A p.Gly312Glu missense_variant 4/102 NM_001350921.2 P2

Frequencies

GnomAD3 genomes
AF:
0.00246
AC:
374
AN:
152202
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000869
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00372
Gnomad FIN
AF:
0.00141
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00412
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00275
AC:
691
AN:
251470
Hom.:
3
AF XY:
0.00286
AC XY:
389
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.000800
Gnomad AMR exome
AF:
0.00176
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00372
Gnomad FIN exome
AF:
0.00185
Gnomad NFE exome
AF:
0.00396
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00374
AC:
5467
AN:
1461894
Hom.:
19
Cov.:
34
AF XY:
0.00373
AC XY:
2709
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000747
Gnomad4 AMR exome
AF:
0.00174
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00385
Gnomad4 FIN exome
AF:
0.00137
Gnomad4 NFE exome
AF:
0.00427
Gnomad4 OTH exome
AF:
0.00315
GnomAD4 genome
AF:
0.00246
AC:
374
AN:
152320
Hom.:
1
Cov.:
33
AF XY:
0.00250
AC XY:
186
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.000866
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00373
Gnomad4 FIN
AF:
0.00141
Gnomad4 NFE
AF:
0.00412
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00372
Hom.:
3
Bravo
AF:
0.00250
TwinsUK
AF:
0.00431
AC:
16
ALSPAC
AF:
0.00415
AC:
16
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00442
AC:
38
ExAC
AF:
0.00255
AC:
310
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00447
EpiControl
AF:
0.00433

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
1.1
DANN
Benign
0.60
DEOGEN2
Benign
0.0047
T;T;.;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.098
N
LIST_S2
Benign
0.70
T;T;T;T
M_CAP
Benign
0.0042
T
MetaRNN
Benign
0.0058
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N
PROVEAN
Benign
0.60
N;N;N;.
REVEL
Benign
0.017
Sift
Benign
0.34
T;T;T;.
Sift4G
Benign
0.53
T;T;T;.
Polyphen
0.23
B;.;.;.
Vest4
0.21
MVP
0.13
MPC
0.10
ClinPred
0.00064
T
GERP RS
-0.35
Varity_R
0.036
gMVP
0.059

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

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

Other links and lift over

dbSNP: rs145052480; hg19: chr10-128193125; API