rs869025342

Positions:

• chr3-14671194-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The ENST00000383794.7(CCDC174):​c.1404A>G​(p.Ter468TrpextTer6) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC174 ENST00000383794.7 stop_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.10

Genes affected

CCDC174 (HGNC:28033): (coiled-coil domain containing 174) The protein encoded by this gene is found in the nucleus, where it interacts with eukaryotic translation initiation factor 4A, isoform 3. The encoded protein appears to be a part of the exon junction complex, which is involved in RNA processing, translation, and nonsense-mediated mRNA decay. A mutation in this gene has been associated with infantile hypotonia with psychomotor retardation. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in ENST00000383794.7 Downstream stopcodon found after 492 codons.
• PP5: Variant 3-14671194-A-G is Pathogenic according to our data. Variant chr3-14671194-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 222080.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC174	NM_016474.5	c.1404A>G	p.Ter468TrpextTer6	stop_lost	11/11	ENST00000383794.7	NP_057558.3
CCDC174	NM_001410719.1	c.1176A>G	p.Ter392TrpextTer6	stop_lost	9/9		NP_001397648.1
CCDC174	NR_135523.2	n.1384A>G		non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC174	ENST00000383794.7	c.1404A>G	p.Ter468TrpextTer6	stop_lost	11/11	1	NM_016474.5	ENSP00000373304	P1
CCDC174	ENST00000303688.8	c.1176A>G	p.Ter392TrpextTer6	stop_lost	9/9	5		ENSP00000302344

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 18, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.86
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
MutationTaster	Benign	1.0	N;N
Vest4		0.0060
GERP RS		5.4

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: rs869025342; hg19: chr3-14712701;