Variant 3-14654515-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016474.5(CCDC174):c.132A>G(p.Pro44Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000537 in 1,508,744 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

CCDC174
NM_016474.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.871

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 Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 3-14654515-A-G is Benign according to our data. Variant chr3-14654515-A-G is described in ClinVar as [Benign]. Clinvar id is 729670.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.871 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC174	NM_016474.5 linkuse as main transcript	c.132A>G	p.Pro44Pro	synonymous_variant	2/11	ENST00000383794.7	NP_057558.3	Q6PII3
CCDC174	NM_001410719.1 linkuse as main transcript	c.132A>G	p.Pro44Pro	synonymous_variant	2/9		NP_001397648.1
CCDC174	XM_017006555.3 linkuse as main transcript	c.132A>G	p.Pro44Pro	synonymous_variant	2/8		XP_016862044.1
CCDC174	NR_135523.2 linkuse as main transcript	n.207A>G		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC174	ENST00000383794.7 linkuse as main transcript	c.132A>G	p.Pro44Pro	synonymous_variant	2/11	1	NM_016474.5	ENSP00000373304.3	Q6PII3
CCDC174	ENST00000465759.1 linkuse as main transcript	n.196A>G		non_coding_transcript_exon_variant	2/7	1
CCDC174	ENST00000303688.8 linkuse as main transcript	c.132A>G	p.Pro44Pro	synonymous_variant	2/9	5		ENSP00000302344.7	A0A0B4J1R8
CCDC174	ENST00000463438.5 linkuse as main transcript	n.205A>G		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

416

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00955

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000770

AC:

179

AN:

232484

Hom.:

AF XY:

0.000516

AC XY:

AN XY:

125932

show subpopulations

Gnomad AFR exome

AF:

0.0111

Gnomad AMR exome

AF:

0.000474

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000375

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.000288

AC:

391

AN:

1356394

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

133

AN XY:

679792

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

Gnomad4 AMR exome

AF:

0.000405

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000867

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.77e-7

Gnomad4 OTH exome

AF:

0.000722

GnomAD4 genome

AF:

0.00275

AC:

419

AN:

152350

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

188

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00959

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00324

Asia WGS

AF:

0.000579

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.4

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

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