12-95869485-T-C

Position:

• chr12-95869485-T-C

Variant summary

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

The NM_182496.3(CCDC38):​c.1573A>G​(p.Lys525Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC38 NM_182496.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC38	NM_182496.3	c.1573A>G	p.Lys525Glu	missense_variant	15/16	ENST00000344280.8	NP_872302.2
CCDC38	XM_011537883.3	c.1573A>G	p.Lys525Glu	missense_variant	15/16		XP_011536185.1
CCDC38	XM_047428281.1	c.1081A>G	p.Lys361Glu	missense_variant	11/12		XP_047284237.1
CCDC38	XM_011537888.4	c.922A>G	p.Lys308Glu	missense_variant	9/10		XP_011536190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC38	ENST00000344280.8	c.1573A>G	p.Lys525Glu	missense_variant	15/16	1	NM_182496.3	ENSP00000345470.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

May 31, 2023

The c.1573A>G (p.K525E) alteration is located in exon 15 (coding exon 14) of the CCDC38 gene. This alteration results from a A to G substitution at nucleotide position 1573, causing the lysine (K) at amino acid position 525 to be replaced by a glutamic acid (E). 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	0.26
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	-0.0019	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.25	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.35		Loss of sheet (P = 0.003);
MVP		0.82
MPC		0.38
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.71
gMVP		0.52

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: chr12-96263263;