rs777579120

Variant names:

• chr4-24808501-T-A
• rs777579120
• NM_001395273.1:c.1496A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-24808501-T-A
• chr4-24808501-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395273.1(CCDC149):​c.1496A>T​(p.Lys499Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign 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. K499T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC149 NM_001395273.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054601997).

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.1496A>T	p.Lys499Ile	missense	Exon 13 of 13	NP_001382202.1	A0A0U1RQD2
	CCDC149	NM_173463.6		c.1478A>T	p.Lys493Ile	missense	Exon 13 of 13	NP_775734.2	Q6ZUS6-5
	CCDC149	NM_001130726.5		c.1463A>T	p.Lys488Ile	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.1496A>T	p.Lys499Ile	missense	Exon 13 of 13	ENSP00000488929.2	A0A0U1RQD2
	CCDC149	ENST00000502801.1	TSL:1	c.*265A>T		3_prime_UTR	Exon 5 of 5	ENSP00000427529.2	A0A8V8PVV8
	CCDC149	ENST00000904727.1		c.1487A>T	p.Lys496Ile	missense	Exon 13 of 13	ENSP00000574786.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 130058 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0090
DANN	Benign	0.48
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.4
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.021
Sift	Benign	0.034	D
Sift4G	Benign	0.061	T
Vest4		0.22
MVP		0.12
MPC		1.0
ClinPred		0.084	T
GERP RS		-11
gMVP		0.066
Mutation Taster		=97/3	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: rs777579120; hg19: chr4-24810123;