17-16690692-C-T

Variant names:

• chr17-16690692-C-T
• rs561026830
• NM_001382000.1:c.292C>T

Variant summary

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

The NM_001382000.1(CCDC144A):​c.292C>T​(p.His98Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000656 in 152,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. H98N) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: CCDC144A NM_001382000.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 0 publications found

Genes affected

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

ENSG00000266302 (HGNC:):

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=0.05741349).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382000.1. 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
	CCDC144A	NM_001382000.1	MANE Select	c.292C>T	p.His98Tyr	missense	Exon 1 of 17	NP_001368929.1	C9JT67
	CCDC144A	NM_014695.3		c.292C>T	p.His98Tyr	missense	Exon 1 of 18	NP_055510.1	A2RUR9-1
	CCDC144A	NR_130142.2		n.452C>T		non_coding_transcript_exon	Exon 1 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC144A	ENST00000399273.5	TSL:1 MANE Select	c.292C>T	p.His98Tyr	missense	Exon 1 of 17	ENSP00000382215.1	C9JT67
	CCDC144A	ENST00000360524.12	TSL:1	c.292C>T	p.His98Tyr	missense	Exon 1 of 18	ENSP00000353717.8	A2RUR9-1
	CCDC144A	ENST00000360495.9	TSL:1	n.292C>T		non_coding_transcript_exon	Exon 1 of 16	ENSP00000353685.5	A6NG92

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250608 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 AF: 0.00000656 AC: 1 AN: 152332 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.88
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.046
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.050
Sift	Benign	0.11	T
Sift4G	Uncertain	0.018	D
Polyphen		0.11	B
Vest4		0.25
MutPred		0.40		Gain of phosphorylation at H98 (P = 0.0181)
MVP		0.030
ClinPred		0.029	T
GERP RS		0.54
PromoterAI		0.0054	Neutral
Varity_R		0.069
gMVP		0.028
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: rs561026830; hg19: chr17-16594006;