Variant chr12-95872386-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182496.3(CCDC38):c.1353C>A(p.Asp451Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CCDC38
NM_182496.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.711

Variant links:

Genes affected

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

CCDC38 links:

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]

SNRPF links:

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ACMG classification

Classification made for transcript

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=0.073186606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC38	NM_182496.3 linkuse as main transcript	c.1353C>A	p.Asp451Glu	missense_variant	14/16	ENST00000344280.8	NP_872302.2	Q502W7
CCDC38	XM_011537883.3 linkuse as main transcript	c.1353C>A	p.Asp451Glu	missense_variant	14/16		XP_011536185.1	Q502W7
CCDC38	XM_047428281.1 linkuse as main transcript	c.861C>A	p.Asp287Glu	missense_variant	10/12		XP_047284237.1
CCDC38	XM_011537888.4 linkuse as main transcript	c.702C>A	p.Asp234Glu	missense_variant	8/10		XP_011536190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC38	ENST00000344280.8 linkuse as main transcript	c.1353C>A	p.Asp451Glu	missense_variant	14/16	1	NM_182496.3	ENSP00000345470.3	Q502W7
SNRPF	ENST00000552085.1 linkuse as main transcript	c.130-7302G>T		intron_variant		3		ENSP00000447127.1	F8W0W6
SNRPF	ENST00000553192.5 linkuse as main transcript	c.130-7302G>T		intron_variant		4		ENSP00000447751.1	A0A0B4J254
CCDC38	ENST00000549876.5 linkuse as main transcript	n.237C>A		non_coding_transcript_exon_variant	3/5	5		ENSP00000447129.1	H0YHI1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1353C>A (p.D451E) alteration is located in exon 14 (coding exon 13) of the CCDC38 gene. This alteration results from a C to A substitution at nucleotide position 1353, causing the aspartic acid (D) at amino acid position 451 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.00072

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.61

M_CAP

Benign

0.012

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.080

REVEL

Benign

0.026

Sift

Benign

0.083

Sift4G

Benign

1.0

Polyphen

0.51

Vest4

0.058

MutPred

0.19

Loss of catalytic residue at D451 (P = 0.1766);

MVP

0.072

MPC

0.077

ClinPred

0.19

GERP RS

2.6

Varity_R

0.050

gMVP

0.079

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over