chr4-24808400-C-T

Variant names:

• chr4-24808400-C-T
• rs193242333
• NM_001395273.1:c.1597G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395273.1(CCDC149):​c.1597G>A​(p.Val533Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,449,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V533L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000099 (0 hom.)
• Consequence: CCDC149 NM_001395273.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.70
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0046538115).

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.1597G>A	p.Val533Met	missense	Exon 13 of 13	NP_001382202.1	A0A0U1RQD2
	CCDC149	NM_173463.6		c.1579G>A	p.Val527Met	missense	Exon 13 of 13	NP_775734.2	Q6ZUS6-5
	CCDC149	NM_001130726.5		c.1564G>A	p.Val522Met	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.1597G>A	p.Val533Met	missense	Exon 13 of 13	ENSP00000488929.2	A0A0U1RQD2
	CCDC149	ENST00000502801.1	TSL:1	c.*366G>A		3_prime_UTR	Exon 5 of 5	ENSP00000427529.2	A0A8V8PVV8
	CCDC149	ENST00000904727.1		c.1588G>A	p.Val530Met	missense	Exon 13 of 13	ENSP00000574786.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000110 AC: 9 AN: 81776 AF XY: 0.000151

Gnomad AFR exome AF: 0.000140

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000740

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000987 AC: 128 AN: 1297400 Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 63 AN XY: 628226

African (AFR) AF: 0.0000708 AC: 2 AN: 28254

American (AMR) AF: 0.000105 AC: 2 AN: 19018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18826

East Asian (EAS) AF: 0.00239 AC: 83 AN: 34660

South Asian (SAS) AF: 0.000280 AC: 17 AN: 60808

European-Finnish (FIN) AF: 0.0000219 AC: 1 AN: 45706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5220

European-Non Finnish (NFE) AF: 0.0000175 AC: 18 AN: 1031302

Other (OTH) AF: 0.0000933 AC: 5 AN: 53606

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74490

African (AFR) AF: 0.000216 AC: 9 AN: 41600

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

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

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000845 Hom.: 1

Bravo AF: 0.000151

ExAC AF: 0.000148 AC: 3

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	0.074
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.021
DANN	Benign	0.76
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.7
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.0070
Sift	Benign	0.050	D
Sift4G	Uncertain	0.025	D
Vest4		0.064
MVP		0.055
MPC		0.59
ClinPred		0.018	T
GERP RS		-6.5
gMVP		0.055
Mutation Taster		=99/1	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: rs193242333; hg19: chr4-24810022;