3-14661475-C-A

Position:

• chr3-14661475-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016474.5(CCDC174):​c.308-55C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.888 in 1,492,360 control chromosomes in the GnomAD database, including 590,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52818 hom., cov: 32)
  • Exomes 𝑓: 0.89 (537653 hom.)
• Consequence: CCDC174 NM_016474.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00300

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]

CCDC174 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-14661475-C-A is Benign according to our data. Variant chr3-14661475-C-A is described in ClinVar as [Benign]. Clinvar id is 1192653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC174	NM_016474.5	c.308-55C>A		intron_variant		ENST00000383794.7	NP_057558.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC174	ENST00000383794.7	c.308-55C>A		intron_variant		1	NM_016474.5	ENSP00000373304.3
CCDC174	ENST00000465759.1	n.372-55C>A		intron_variant		1
CCDC174	ENST00000303688.8	c.308-55C>A		intron_variant		5		ENSP00000302344.7
CCDC174	ENST00000463438.5	n.381-55C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125718 AN: 152026 Hom.: 52778 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.856

GnomAD4 exome AF: 0.894 AC: 1198667 AN: 1340216 Hom.: 537653 AF XY: 0.896 AC XY: 596242 AN XY: 665430

Gnomad4 AFR exome AF: 0.685

Gnomad4 AMR exome AF: 0.825

Gnomad4 ASJ exome AF: 0.921

Gnomad4 EAS exome AF: 0.743

Gnomad4 SAS exome AF: 0.912

Gnomad4 FIN exome AF: 0.868

Gnomad4 NFE exome AF: 0.908

Gnomad4 OTH exome AF: 0.886

GnomAD4 genome AF: 0.827 AC: 125809 AN: 152144 Hom.: 52818 Cov.: 32 AF XY: 0.824 AC XY: 61298 AN XY: 74392

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.716

Gnomad4 SAS AF: 0.906

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.856

Alfa AF: 0.895 Hom.: 105052

Bravo AF: 0.818

Asia WGS AF: 0.822 AC: 2859 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.77

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: rs2276754; hg19: chr3-14702982; COSMIC: COSV57979720;