17-16705348-C-T

Variant names:

• chr17-16705348-C-T
• rs531081500
• NM_001382000.1:c.613C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382000.1(CCDC144A):​c.613C>T​(p.Leu205Phe) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: CCDC144A NM_001382000.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0630

Genes affected

CCDC144A (HGNC:29072): (coiled-coil domain containing 144A)

ENSG00000266302 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.012252271).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC144A	NM_001382000.1	c.613C>T	p.Leu205Phe	missense_variant	Exon 3 of 17	ENST00000399273.5	NP_001368929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC144A	ENST00000399273.5	c.613C>T	p.Leu205Phe	missense_variant	Exon 3 of 17	1	NM_001382000.1	ENSP00000382215.1
ENSG00000266302	ENST00000448331.7	n.613C>T		non_coding_transcript_exon_variant	Exon 3 of 26	2		ENSP00000440655.2

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150756 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000245

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

GnomAD3 exomes AF: 0.0000171 AC: 1 AN: 58498 Hom.: 0 AF XY: 0.0000341 AC XY: 1 AN XY: 29352

Gnomad AFR exome AF: 0.000182

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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.: 9

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ExAC AF: 0.0000717 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.613C>T (p.L205F) alteration is located in exon 3 (coding exon 3) of the CCDC144A gene. This alteration results from a C to T substitution at nucleotide position 613, causing the leucine (L) at amino acid position 205 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0046	.;.;.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.012	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.047
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Pathogenic	0.0	D;T;D;T
Polyphen		0.98	.;.;.;D
Vest4		0.28
MutPred		0.31		Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);
MVP		0.061
ClinPred		0.033	T
GERP RS		0.76
Varity_R		0.069
gMVP		0.0081

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

Publications

LitVar

Other links and lift over

dbSNP: rs531081500; hg19: chr17-16608662;