rs2281878

chr10-102450978-C-Achr10-102450978-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363580.1(C10orf95):c.116G>T(p.Ser39Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,295,332 control chromosomes in the GnomAD database, including 31,938 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/11 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 0.22 (3987 hom., cov: 32)
  • Exomes 𝑓: 0.22 (27951 hom.)
• Consequence: C10orf95 NM_001363580.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

Genes affected

C10orf95 (HGNC:25880): (chromosome 10 open reading frame 95)

C10orf95-AS1 (HGNC:45238): (C10orf95 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045433044).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C10orf95	NM_001363580.1	c.116G>T	p.Ser39Ile	missense_variant	2/2	ENST00000625129.1
C10orf95-AS1	NR_038937.1	n.381-421C>A		intron_variant, non_coding_transcript_variant
C10orf95-AS1	NR_038938.1	n.350+648C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C10orf95	ENST00000625129.1	c.116G>T	p.Ser39Ile	missense_variant	2/2	1	NM_001363580.1	P1
C10orf95-AS1	ENST00000594818.1	n.138+648C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34005 AN: 152008 Hom.: 3980 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.204

GnomAD3 exomes AF: 0.237 AC: 18304 AN: 77240 Hom.: 2315 AF XY: 0.235 AC XY: 10471 AN XY: 44628

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.369

Gnomad SAS exome AF: 0.334

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.217 AC: 247697 AN: 1143208 Hom.: 27951 Cov.: 32 AF XY: 0.217 AC XY: 118625 AN XY: 547388

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.372

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.224 AC: 34035 AN: 152124 Hom.: 3987 Cov.: 32 AF XY: 0.225 AC XY: 16703 AN XY: 74346

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.205

Alfa AF: 0.211 Hom.: 543

Bravo AF: 0.222

TwinsUK AF: 0.200 AC: 741

ALSPAC AF: 0.210 AC: 811

ESP6500AA AF: 0.203 AC: 686

ESP6500EA AF: 0.183 AC: 1301

ExAC AF: 0.215 AC: 23052

Asia WGS AF: 0.335 AC: 1158 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	17
Dann	Benign	0.96
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0045	T
MutationTaster	Benign	1.0	P
GERP RS		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.10

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2281878; hg19: chr10-104210735; COSMIC: COSV53309120; COSMIC: COSV53309120;