NM_001395273.1:c.1302G>C

Variant names:

• chr4-24808695-C-G
• rs1395356610
• NM_001395273.1:c.1302G>C

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.1302G>C​(p.Lys434Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: CCDC149 NM_001395273.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.237
• 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=0.05544558).

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.1302G>C	p.Lys434Asn	missense	Exon 13 of 13	NP_001382202.1	A0A0U1RQD2
	CCDC149	NM_173463.6		c.1284G>C	p.Lys428Asn	missense	Exon 13 of 13	NP_775734.2	Q6ZUS6-5
	CCDC149	NM_001130726.5		c.1269G>C	p.Lys423Asn	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.1302G>C	p.Lys434Asn	missense	Exon 13 of 13	ENSP00000488929.2	A0A0U1RQD2
	CCDC149	ENST00000502801.1	TSL:1	c.*71G>C		3_prime_UTR	Exon 5 of 5	ENSP00000427529.2	A0A8V8PVV8
	CCDC149	ENST00000904727.1		c.1293G>C	p.Lys431Asn	missense	Exon 13 of 13	ENSP00000574786.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

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: 0.00 AC: 0 AN: 68040

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.8
DANN	Uncertain	0.98
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.24
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.057
Sift	Benign	0.27	T
Sift4G	Benign	0.64	T
Vest4		0.052
MVP		0.040
MPC		0.68
ClinPred		0.040	T
GERP RS		1.5
gMVP		0.15
Mutation Taster		=92/8	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: rs1395356610; hg19: chr4-24810317;