chr12-95895082-T-C

Variant names:

• chr12-95895082-T-C
• rs10859974
• NM_182496.3:c.679A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 24 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182496.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC38	NM_182496.3	MANE Select	c.679A>G	p.Met227Val	missense	Exon 8 of 16	NP_872302.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC38	ENST00000344280.8	TSL:1 MANE Select	c.679A>G	p.Met227Val	missense	Exon 8 of 16	ENSP00000345470.3
	SNRPF	ENST00000552085.1	TSL:3	c.286+5901T>C		intron	N/A	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

GnomAD2 exomes AF: 0.198 AC: 49611 AN: 249968 AF XY: 0.195

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

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

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

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: 57 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11981 AN: 67970

Other (OTH) AF: 0.223 AC: 470 AN: 2108

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 v4.9

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
PhyloP100		-0.048
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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