NM_001395273.1:c.1000G>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

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

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.1000G>A	p.Glu334Lys	missense	Exon 10 of 13	NP_001382202.1	A0A0U1RQD2
	CCDC149	NM_173463.6		c.1015G>A	p.Glu339Lys	missense	Exon 11 of 13	NP_775734.2	Q6ZUS6-5
	CCDC149	NM_001130726.5		c.1000G>A	p.Glu334Lys	missense	Exon 10 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.1000G>A	p.Glu334Lys	missense	Exon 10 of 13	ENSP00000488929.2	A0A0U1RQD2
	CCDC149	ENST00000502801.1	TSL:1	c.358-13705G>A		intron	N/A	ENSP00000427529.2	A0A8V8PVV8
	CCDC149	ENST00000904727.1		c.991G>A	p.Glu331Lys	missense	Exon 10 of 13	ENSP00000574786.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Pathogenic	0.96
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
M_CAP	Benign	0.030	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.37	T
PhyloP100		7.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Vest4		0.84
MVP		0.25
MPC		1.6
ClinPred		0.99	D
GERP RS		5.8
gMVP		0.56
Mutation Taster		=4/96	disease causing

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

Other links and lift over

hg19: chr4-24824146;