chr3-107377786-C-A

Variant names:

• chr3-107377786-C-A
• NM_032600.3:c.199C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_032600.3(CCDC54):​c.199C>A​(p.Pro67Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC54 NM_032600.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0670

Genes affected

CCDC54 (HGNC:30703): (coiled-coil domain containing 54)

CCDC54-AS1 (HGNC:56107): (CCDC54 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02621612).
• BP6: Variant 3-107377786-C-A is Benign according to our data. Variant chr3-107377786-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3828668.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC54	NM_032600.3	c.199C>A	p.Pro67Thr	missense_variant	Exon 1 of 1	ENST00000261058.3	NP_115989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC54	ENST00000261058.3	c.199C>A	p.Pro67Thr	missense_variant	Exon 1 of 1	6	NM_032600.3	ENSP00000261058.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 13, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.017
DANN	Benign	0.12
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.035
MutPred		0.31		Gain of sheet (P = 0.0149);
MVP		0.15
MPC		0.039
ClinPred		0.072	T
GERP RS		-1.1
Varity_R		0.033
gMVP		0.024

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: chr3-107096633;