4-24831524-T-G

Variant names:

• chr4-24831524-T-G
• rs1716147336
• NM_001395273.1:c.932A>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001395273.1(CCDC149):​c.932A>C​(p.His311Pro) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H311R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC149 NM_001395273.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.92
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.945

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.932A>C	p.His311Pro	missense	Exon 9 of 13	NP_001382202.1	A0A0U1RQD2
	CCDC149	NM_173463.6		c.947A>C	p.His316Pro	missense	Exon 10 of 13	NP_775734.2	Q6ZUS6-5
	CCDC149	NM_001130726.5		c.932A>C	p.His311Pro	missense	Exon 9 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.932A>C	p.His311Pro	missense	Exon 9 of 13	ENSP00000488929.2	A0A0U1RQD2
	CCDC149	ENST00000502801.1	TSL:1	c.357+21548A>C		intron	N/A	ENSP00000427529.2	A0A8V8PVV8
	CCDC149	ENST00000904727.1		c.923A>C	p.His308Pro	missense	Exon 9 of 13	ENSP00000574786.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	32
DANN	Uncertain	0.98
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.026	D
PhyloP100		7.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-9.3	D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Vest4		0.98
MVP		0.30
MPC		1.9
ClinPred		1.0	D
GERP RS		5.4
gMVP		0.66
Mutation Taster		=7/93	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

dbSNP: rs1716147336; hg19: chr4-24833146;