chr12-95878246-G-T

Position:

• chr12-95878246-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182496.3(CCDC38):​c.1243C>A​(p.Leu415Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC38 NM_182496.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32843548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC38	NM_182496.3	c.1243C>A	p.Leu415Ile	missense_variant	13/16	ENST00000344280.8	NP_872302.2
CCDC38	XM_011537883.3	c.1243C>A	p.Leu415Ile	missense_variant	13/16		XP_011536185.1
CCDC38	XM_047428281.1	c.751C>A	p.Leu251Ile	missense_variant	9/12		XP_047284237.1
CCDC38	XM_011537888.4	c.592C>A	p.Leu198Ile	missense_variant	7/10		XP_011536190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC38	ENST00000344280.8	c.1243C>A	p.Leu415Ile	missense_variant	13/16	1	NM_182496.3	ENSP00000345470.3
SNRPF	ENST00000552085.1	c.130-1442G>T		intron_variant		3		ENSP00000447127.1
SNRPF	ENST00000553192.5	c.130-1442G>T		intron_variant		4		ENSP00000447751.1
CCDC38	ENST00000549876.5	n.127C>A		non_coding_transcript_exon_variant	2/5	5		ENSP00000447129.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461184 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726912

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Sep 20, 2023

The c.1243C>A (p.L415I) alteration is located in exon 13 (coding exon 12) of the CCDC38 gene. This alteration results from a C to A substitution at nucleotide position 1243, causing the leucine (L) at amino acid position 415 to be replaced by an isoleucine (I). 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	0.13
BayesDel_addAF	Benign	-0.0013	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0023	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.19		Loss of ubiquitination at K414 (P = 0.0486);
MVP		0.27
MPC		0.35
ClinPred		0.88	D
GERP RS		5.8
Varity_R		0.081
gMVP		0.081

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: chr12-96272024;