Genetic Variant C10orf95:p.Ser39Ile (chr10-102450978-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.198

Publications

13 publications found

Variant links:

Genes affected

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

C10orf95 links:

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

C10orf95-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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	A0A1B0GTG0
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

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	A0A1B0GTG0
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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.217

AC XY:

118625

AN XY:

547388

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

12727

25455

38182

50910

63637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7968

15936

23904

31872

39840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.224

AC:

34035

AN:

152124

Hom.:

3987

Cov.:

AF XY:

0.225

AC XY:

16703

AN XY:

74346

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.208

AC:

14121

AN:

67952

Other (OTH)

AF:

0.205

AC:

432

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1369

2738

4106

5475

6844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.96

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0045

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)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over