chr4-24808494-G-T

Position:

• chr4-24808494-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395273.1(CCDC149):​c.1503C>A​(p.His501Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000443 in 1,354,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: CCDC149 NM_001395273.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09

Genes affected

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

ACMG classification

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=0.07148293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC149	NM_001395273.1	c.1503C>A	p.His501Gln	missense_variant	13/13	ENST00000635206.3	NP_001382202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC149	ENST00000635206.3	c.1503C>A	p.His501Gln	missense_variant	13/13	5	NM_001395273.1	ENSP00000488929.2
CCDC149	ENST00000502801.1	c.*272C>A		3_prime_UTR_variant	5/5	1		ENSP00000427529.2
CCDC149	ENST00000389609.8	c.1485C>A	p.His495Gln	missense_variant	13/13	2		ENSP00000374260.4
CCDC149	ENST00000504487.5	c.1470C>A	p.His490Gln	missense_variant	12/12	2		ENSP00000425715.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000443 AC: 6 AN: 1354642 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 663826

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: 0.00000566

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Jun 25, 2024

The c.1485C>A (p.H495Q) alteration is located in exon 13 (coding exon 12) of the CCDC149 gene. This alteration results from a C to A substitution at nucleotide position 1485, causing the histidine (H) at amino acid position 495 to be replaced by a glutamine (Q). 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	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.1
DANN	Benign	0.52
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.45	T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.0	N;.;N
REVEL	Benign	0.031
Sift	Benign	0.30	T;.;T
Sift4G	Benign	0.38	T;T;T
Vest4		0.051
MVP		0.055
MPC		0.57
ClinPred		0.11	T
GERP RS		2.6
gMVP		0.041

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: chr4-24810116;