10-102450978-C-A

Variant names:

• chr10-102450978-C-A
• rs2281878
• NM_001363580.1:c.116G>T

Variant summary

Our verdict is Benign. The variant received -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. 8/12 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
• Publications: 13 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363580.1. 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
	C10orf95	NM_001363580.1	MANE Select	c.116G>T	p.Ser39Ile	missense	Exon 2 of 2	NP_001350509.1
	C10orf95-AS1	NR_038937.1		n.381-421C>A		intron	N/A
	C10orf95-AS1	NR_038938.1		n.350+648C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C10orf95	ENST00000625129.1	TSL:1 MANE Select	c.116G>T	p.Ser39Ile	missense	Exon 2 of 2	ENSP00000489684.1
	C10orf95-AS1	ENST00000473970.4	TSL:1	n.351+648C>A		intron	N/A
	C10orf95-AS1	ENST00000492465.2	TSL:1	n.345-421C>A		intron	N/A

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

GnomAD2 exomes AF: 0.237 AC: 18304 AN: 77240 AF XY: 0.235

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 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

African (AFR) AF: 0.225 AC: 5575 AN: 24754

American (AMR) AF: 0.213 AC: 3449 AN: 16192

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 3261 AN: 15194

East Asian (EAS) AF: 0.372 AC: 11219 AN: 30172

South Asian (SAS) AF: 0.338 AC: 9365 AN: 27682

European-Finnish (FIN) AF: 0.214 AC: 5711 AN: 26744

Middle Eastern (MID) AF: 0.195 AC: 818 AN: 4204

European-Non Finnish (NFE) AF: 0.208 AC: 198090 AN: 952372

Other (OTH) AF: 0.222 AC: 10209 AN: 45894

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

African (AFR) AF: 0.232 AC: 9647 AN: 41532

American (AMR) AF: 0.206 AC: 3150 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3470

East Asian (EAS) AF: 0.343 AC: 1763 AN: 5136

South Asian (SAS) AF: 0.344 AC: 1661 AN: 4828

European-Finnish (FIN) AF: 0.210 AC: 2222 AN: 10592

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14121 AN: 67952

Other (OTH) AF: 0.205 AC: 432 AN: 2112

Alfa AF: 0.220 Hom.: 1251

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
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
PhyloP100		-0.20
GERP RS		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
gMVP		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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