10-126504416-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350921.2(C10orf90):​c.1075G>A​(p.Asp359Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,613,930 control chromosomes in the GnomAD database, including 93,769 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.40 (13894 hom., cov: 32)
  • Exomes 𝑓: 0.32 (79875 hom.)
• Consequence: C10orf90 NM_001350921.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 29 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.0354714E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350921.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C10orf90	NM_001350921.2	MANE Select	c.1075G>A	p.Asp359Asn	missense	Exon 4 of 10	NP_001337850.1
	C10orf90	NM_001004298.4		c.784G>A	p.Asp262Asn	missense	Exon 3 of 9	NP_001004298.2
	C10orf90	NM_001350922.2		c.1075G>A	p.Asp359Asn	missense	Exon 4 of 9	NP_001337851.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C10orf90	ENST00000488181.3	TSL:2 MANE Select	c.1075G>A	p.Asp359Asn	missense	Exon 4 of 10	ENSP00000474558.3
	C10orf90	ENST00000284694.11	TSL:1	c.784G>A	p.Asp262Asn	missense	Exon 3 of 9	ENSP00000284694.7
	C10orf90	ENST00000432642.5	TSL:2	c.784G>A	p.Asp262Asn	missense	Exon 3 of 8	ENSP00000405995.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61014 AN: 151928 Hom.: 13856 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.372 AC: 93548 AN: 251316 AF XY: 0.368

Gnomad AFR exome AF: 0.621

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.510

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.340

GnomAD4 exome AF: 0.321 AC: 469720 AN: 1461884 Hom.: 79875 Cov.: 56 AF XY: 0.324 AC XY: 235296 AN XY: 727242

African (AFR) AF: 0.632 AC: 21168 AN: 33480

American (AMR) AF: 0.434 AC: 19391 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 9526 AN: 26136

East Asian (EAS) AF: 0.487 AC: 19349 AN: 39700

South Asian (SAS) AF: 0.451 AC: 38944 AN: 86258

European-Finnish (FIN) AF: 0.270 AC: 14416 AN: 53420

Middle Eastern (MID) AF: 0.350 AC: 2017 AN: 5768

European-Non Finnish (NFE) AF: 0.291 AC: 323924 AN: 1112004

Other (OTH) AF: 0.347 AC: 20985 AN: 60396

GnomAD4 genome AF: 0.402 AC: 61113 AN: 152046 Hom.: 13894 Cov.: 32 AF XY: 0.403 AC XY: 29979 AN XY: 74320

African (AFR) AF: 0.612 AC: 25372 AN: 41458

American (AMR) AF: 0.400 AC: 6122 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1237 AN: 3466

East Asian (EAS) AF: 0.503 AC: 2590 AN: 5150

South Asian (SAS) AF: 0.465 AC: 2239 AN: 4816

European-Finnish (FIN) AF: 0.259 AC: 2746 AN: 10582

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19742 AN: 67972

Other (OTH) AF: 0.381 AC: 804 AN: 2112

Alfa AF: 0.339 Hom.: 21039

Bravo AF: 0.423

TwinsUK AF: 0.295 AC: 1095

ALSPAC AF: 0.298 AC: 1147

ESP6500AA AF: 0.595 AC: 2620

ESP6500EA AF: 0.302 AC: 2596

ExAC AF: 0.374 AC: 45369

Asia WGS AF: 0.494 AC: 1716 AN: 3478

EpiCase AF: 0.302

EpiControl AF: 0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.70
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000060	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.1	N
PhyloP100		1.6
PROVEAN	Benign	1.1	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.053
MPC		0.074
ClinPred		0.00030	T
GERP RS		1.6
PromoterAI		0.0048	Neutral
Varity_R		0.025
gMVP		0.056
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV52949554; COSMIC: COSV52949554;