dbSNP rs10859974: CCDC38:p.Met227Val (chr12-95895082-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_182496.3(CCDC38):c.679A>G(p.Met227Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,611,748 control chromosomes in the GnomAD database, including 30,095 homozygotes. 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: 𝑓 0.22 ( 3849 hom., cov: 32)

Exomes 𝑓: 0.18 ( 26246 hom. )

Consequence

CCDC38
NM_182496.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0480

Publications

24 publications found

Variant links:

Genes affected

CCDC38 (HGNC:26843): (coiled-coil domain containing 38) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CCDC38 links:

SNRPF (HGNC:11162): (small nuclear ribonucleoprotein polypeptide F) Enables RNA binding activity. Involved in spliceosomal snRNP assembly. Located in cytosol and nucleus. Part of several cellular components, including methylosome; nucleus; and pICln-Sm protein complex. Biomarker of nasopharynx carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

SNRPF 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=0.0041117966).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC38	NM_182496.3 link	c.679A>G	p.Met227Val	missense_variant	Exon 8 of 16	ENST00000344280.8	NP_872302.2	Q502W7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC38	ENST00000344280.8 link	c.679A>G	p.Met227Val	missense_variant	Exon 8 of 16	1	NM_182496.3	ENSP00000345470.3		Q502W7
SNRPF	ENST00000552085.1 link	c.286+5901T>C		intron_variant	Intron 4 of 4	3		ENSP00000447127.1		F8W0W6

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32905

AN:

151924

Hom.:

3846

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.163

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.425

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.218

GnomAD2 exomes

AF:

0.198

AC:

49611

AN:

249968

AF XY:

0.195

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.0981

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.420

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.181

AC:

264259

AN:

1459706

Hom.:

26246

Cov.:

AF XY:

0.180

AC XY:

130738

AN XY:

726158

show subpopulations

African (AFR)

AF:

0.272

AC:

9077

AN:

33376

American (AMR)

AF:

0.105

AC:

4653

AN:

44522

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

5636

AN:

26100

East Asian (EAS)

AF:

0.417

AC:

16482

AN:

39534

South Asian (SAS)

AF:

0.138

AC:

11879

AN:

85840

European-Finnish (FIN)

AF:

0.275

AC:

14694

AN:

53368

Middle Eastern (MID)

AF:

0.182

AC:

1050

AN:

5762

European-Non Finnish (NFE)

AF:

0.170

AC:

189088

AN:

1110906

Other (OTH)

AF:

0.194

AC:

11700

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

9613

19225

28838

38450

48063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.217

AC:

32938

AN:

152042

Hom.:

3849

Cov.:

AF XY:

0.219

AC XY:

16283

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.270

AC:

11185

AN:

41462

American (AMR)

AF:

0.163

AC:

2490

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

708

AN:

3472

East Asian (EAS)

AF:

0.426

AC:

2199

AN:

5164

South Asian (SAS)

AF:

0.152

AC:

734

AN:

4822

European-Finnish (FIN)

AF:

0.280

AC:

2956

AN:

10566

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11981

AN:

67970

Other (OTH)

AF:

0.223

AC:

470

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1312

2624

3935

5247

6559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.191

Hom.:

5714

Bravo

AF:

0.214

TwinsUK

AF:

0.177

AC:

656

ALSPAC

AF:

0.168

AC:

647

ESP6500AA

AF:

0.271

AC:

1194

ESP6500EA

AF:

0.173

AC:

1489

ExAC

AF:

0.202

AC:

24531

Asia WGS

AF:

0.288

AC:

1001

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.8

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0082

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.2

PhyloP100

-0.048

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.72

REVEL

Benign

0.089

Sift

Benign

0.13

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.050

MPC

0.054

ClinPred

0.0049

GERP RS

-1.6

Varity_R

0.058

gMVP

0.31

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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rs10859974

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over