rs10859974

Positions:

• chr12-95895082-T-C

Variant summary

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

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. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (3849 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26246 hom.)
• Consequence: CCDC38 NM_182496.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CCDC38	NM_182496.3	c.679A>G	p.Met227Val	missense_variant	8/16	ENST00000344280.8	NP_872302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC38	ENST00000344280.8	c.679A>G	p.Met227Val	missense_variant	8/16	1	NM_182496.3	ENSP00000345470.3
SNRPF	ENST00000552085.1	c.286+5901T>C		intron_variant		3		ENSP00000447127.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32905 AN: 151924 Hom.: 3846 Cov.: 32

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

GnomAD3 exomes AF: 0.198 AC: 49611 AN: 249968 Hom.: 5883 AF XY: 0.195 AC XY: 26290 AN XY: 135112

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 SAS exome AF: 0.134

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.: 31 AF XY: 0.180 AC XY: 130738 AN XY: 726158

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.105

Gnomad4 ASJ exome AF: 0.216

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.217 AC: 32938 AN: 152042 Hom.: 3849 Cov.: 32 AF XY: 0.219 AC XY: 16283 AN XY: 74318

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.223

Alfa AF: 0.185 Hom.: 3559

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	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.8
DANN	Benign	0.73
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.2	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.089
Sift	Benign	0.13	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.050
MPC		0.054
ClinPred		0.0049	T
GERP RS		-1.6
Varity_R		0.058
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs10859974; hg19: chr12-96288860; COSMIC: COSV60182566; COSMIC: COSV60182566;