4-24822524-C-T

Variant names:

• chr4-24822524-C-T
• NM_001395273.1:c.1000G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001395273.1(CCDC149):​c.1000G>A​(p.Glu334Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC149 NM_001395273.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

CCDC149 (HGNC:25405): (coiled-coil domain containing 149)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC149	NM_001395273.1	c.1000G>A	p.Glu334Lys	missense_variant	Exon 10 of 13	ENST00000635206.3	NP_001382202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC149	ENST00000635206.3	c.1000G>A	p.Glu334Lys	missense_variant	Exon 10 of 13	5	NM_001395273.1	ENSP00000488929.2

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

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1015G>A (p.E339K) alteration is located in exon 11 (coding exon 10) of the CCDC149 gene. This alteration results from a G to A substitution at nucleotide position 1015, causing the glutamic acid (E) at amino acid position 339 to be replaced by a lysine (K). 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
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	32
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Benign	-0.37	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.2	D;.;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0040	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.84
MVP		0.25
MPC		1.6
ClinPred		0.99	D
GERP RS		5.8
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr4-24824146;