12-95867153-A-G

Position:

• chr12-95867153-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182496.3(CCDC38):​c.1615T>C​(p.Ser539Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC38 NM_182496.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.180

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]

CCDC38 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.161901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC38	NM_182496.3	c.1615T>C	p.Ser539Pro	missense_variant	16/16	ENST00000344280.8	NP_872302.2
CCDC38	XM_011537883.3	c.1615T>C	p.Ser539Pro	missense_variant	16/16		XP_011536185.1
CCDC38	XM_047428281.1	c.1123T>C	p.Ser375Pro	missense_variant	12/12		XP_047284237.1
CCDC38	XM_011537888.4	c.964T>C	p.Ser322Pro	missense_variant	10/10		XP_011536190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC38	ENST00000344280.8	c.1615T>C	p.Ser539Pro	missense_variant	16/16	1	NM_182496.3	ENSP00000345470.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456372 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724610

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.1615T>C (p.S539P) alteration is located in exon 16 (coding exon 15) of the CCDC38 gene. This alteration results from a T to C substitution at nucleotide position 1615, causing the serine (S) at amino acid position 539 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Benign	0.066	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.20		Loss of sheet (P = 0.003);
MVP		0.21
MPC		0.072
ClinPred		0.57	D
GERP RS		0.43
Varity_R		0.16
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-96260931;