Variant 3-14658932-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The NM_016474.5(CCDC174):c.307+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,505,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CCDC174
NM_016474.5 splice_region, intron

Scores

Splicing: ADA: 0.9871

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.770

Variant links:

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 links:

CCDC174 (HGNC:):

CCDC174 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 3-14658932-A-G is Benign according to our data. Variant chr3-14658932-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052027.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 linkuse as main transcript	c.307+3A>G		splice_region_variant, intron_variant		ENST00000383794.7	NP_057558.3	Q6PII3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CCDC174	ENST00000383794.7 linkuse as main transcript	c.307+3A>G	splice_region_variant, intron_variant	1	NM_016474.5	ENSP00000373304.3	Q6PII3
CCDC174	ENST00000465759.1 linkuse as main transcript	n.371+3A>G	splice_region_variant, intron_variant	1
CCDC174	ENST00000303688.8 linkuse as main transcript	c.307+3A>G	splice_region_variant, intron_variant	5		ENSP00000302344.7	A0A0B4J1R8
CCDC174	ENST00000463438.5 linkuse as main transcript	n.380+3A>G	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

260

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00608

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.00143

GnomAD3 exomes

AF:

0.000389

AC:

AN:

236366

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

128770

show subpopulations

Gnomad AFR exome

AF:

0.00610

Gnomad AMR exome

AF:

0.0000673

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

AF:

0.000156

AC:

211

AN:

1353112

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

670582

show subpopulations

Gnomad4 AFR exome

AF:

0.00590

Gnomad4 AMR exome

AF:

0.000106

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.69e-7

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.00171

AC:

260

AN:

152354

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

103

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00606

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.00193

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CCDC174-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 06, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over