17-20895813-C-G

Variant names:

• chr17-20895813-C-G
• rs147105715
• ENST00000327925.7:n.351G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000327925.7(CCDC144NL):​n.351G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC144NL ENST00000327925.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• Publications: 1 publications found

Genes affected

CCDC144NL (HGNC:):

CCDC144NL-AS1 (HGNC:51340): (CCDC144NL antisense RNA 1)

CCDC144NL (HGNC:33735): (CCDC144A N-terminal like (pseudogene))

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14835039).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000327925.7. 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
	CCDC144NL	NR_164128.1		n.351G>C		non_coding_transcript_exon	Exon 1 of 4
	CCDC144NL-AS1	NR_104185.2		n.362+3381C>G		intron	N/A
	CCDC144NL-AS1	NR_160710.1		n.620+3381C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC144NL	ENST00000327925.7	TSL:1	n.351G>C		non_coding_transcript_exon	Exon 1 of 4
	CCDC144NL-AS1	ENST00000583962.3	TSL:1	n.424+3381C>G		intron	N/A
	CCDC144NL	ENST00000647562.3		n.208G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 251048 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461266 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 726944

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111838

Other (OTH) AF: 0.00 AC: 0 AN: 60332

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.25
PrimateAI	Uncertain	0.54	T
Polyphen		1.0	D
MutPred		0.22		Gain of catalytic residue at L72 (P = 0.0767)
ClinPred		0.20	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.061

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs147105715; hg19: chr17-20799126; COSMIC: COSV60001374; COSMIC: COSV60001374;