NM_001350921.2:c.1075G>T

Variant names:

• chr10-126504416-C-A
• rs11245007
• NM_001350921.2:c.1075G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001350921.2(C10orf90):​c.1075G>T​(p.Asp359Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C10orf90 NM_001350921.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0914928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C10orf90	NM_001350921.2	c.1075G>T	p.Asp359Tyr	missense_variant	Exon 4 of 10	ENST00000488181.3	NP_001337850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C10orf90	ENST00000488181.3	c.1075G>T	p.Asp359Tyr	missense_variant	Exon 4 of 10	2	NM_001350921.2	ENSP00000474558.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 56 AF XY: 0.00 AC XY: 0 AN XY: 727246

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.71
DEOGEN2	Benign	0.040	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.42	T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PhyloP100		1.6
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.053
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		0.053	B;.;.
Vest4		0.33
MVP		0.30
MPC		0.094
ClinPred		0.19	T
GERP RS		1.6
PromoterAI		0.019	Neutral
Varity_R		0.10
gMVP		0.22
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs11245007; hg19: chr10-128192985;