chr4-24808490-C-A

Variant names:

• chr4-24808490-C-A
• rs755084095
• NM_001395273.1:c.1507G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395273.1(CCDC149):​c.1507G>T​(p.Asp503Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,502,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: CCDC149 NM_001395273.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0580
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18504244).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395273.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC149	NM_001395273.1	MANE Select	c.1507G>T	p.Asp503Tyr	missense	Exon 13 of 13	NP_001382202.1	A0A0U1RQD2
	CCDC149	NM_173463.6		c.1489G>T	p.Asp497Tyr	missense	Exon 13 of 13	NP_775734.2	Q6ZUS6-5
	CCDC149	NM_001130726.5		c.1474G>T	p.Asp492Tyr	missense	Exon 12 of 12	NP_001124198.2	A0A8V8PSJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC149	ENST00000635206.3	TSL:5 MANE Select	c.1507G>T	p.Asp503Tyr	missense	Exon 13 of 13	ENSP00000488929.2	A0A0U1RQD2
	CCDC149	ENST00000502801.1	TSL:1	c.*276G>T		3_prime_UTR	Exon 5 of 5	ENSP00000427529.2	A0A8V8PVV8
	CCDC149	ENST00000904727.1		c.1498G>T	p.Asp500Tyr	missense	Exon 13 of 13	ENSP00000574786.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152160 Hom.: 0 Cov.: 33

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000862 AC: 1 AN: 116056 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000213

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000481 AC: 65 AN: 1350558 Hom.: 0 Cov.: 31 AF XY: 0.0000514 AC XY: 34 AN XY: 661340

African (AFR) AF: 0.00 AC: 0 AN: 29616

American (AMR) AF: 0.00 AC: 0 AN: 27324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21754

East Asian (EAS) AF: 0.00 AC: 0 AN: 35400

South Asian (SAS) AF: 0.00 AC: 0 AN: 69468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5424

European-Non Finnish (NFE) AF: 0.0000586 AC: 62 AN: 1058398

Other (OTH) AF: 0.0000537 AC: 3 AN: 55824

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152160 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.058
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.11
Sift	Uncertain	0.010	D
Sift4G	Benign	0.079	T
Vest4		0.28
MVP		0.28
MPC		1.3
ClinPred		0.85	D
GERP RS		3.6
gMVP		0.22
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs755084095; hg19: chr4-24810112;