3-14658929-G-A

Position:

chr3-14658929-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_016474.5(CCDC174):c.307G>A(p.Asp103Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000439 in 1,509,208 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 (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

CCDC174
NM_016474.5 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.54

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:

LOC124906215 (HGNC:):

LOC124906215 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 3-14658929-G-A is Benign according to our data. Variant chr3-14658929-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 709747.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC174	NM_016474.5 linkuse as main transcript	c.307G>A	p.Asp103Asn	missense_variant, splice_region_variant	4/11	ENST00000383794.7	NP_057558.3
LOC124906215	XR_007095827.1 linkuse as main transcript	n.527-139C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCDC174	ENST00000383794.7 linkuse as main transcript	c.307G>A	p.Asp103Asn	missense_variant, splice_region_variant	4/11	1	NM_016474.5	ENSP00000373304	P1
CCDC174	ENST00000465759.1 linkuse as main transcript	n.371G>A		splice_region_variant, non_coding_transcript_exon_variant	4/7	1
CCDC174	ENST00000303688.8 linkuse as main transcript	c.307G>A	p.Asp103Asn	missense_variant, splice_region_variant	4/9	5		ENSP00000302344
CCDC174	ENST00000463438.5 linkuse as main transcript	n.380G>A		splice_region_variant, non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00662

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000438

AC:

105

AN:

239768

Hom.:

AF XY:

0.000314

AC XY:

AN XY:

130438

show subpopulations

Gnomad AFR exome

AF:

0.00564

Gnomad AMR exome

AF:

0.000355

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:

0.0000726

Gnomad OTH exome

AF:

0.000343

GnomAD4 exome

AF:

0.000265

AC:

360

AN:

1356952

Hom.:

Cov.:

AF XY:

0.000210

AC XY:

141

AN XY:

672382

show subpopulations

Gnomad4 AFR exome

AF:

0.00648

Gnomad4 AMR exome

AF:

0.000338

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.000613

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152256

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00660

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000587

Hom.:

Bravo

AF:

0.00215

ESP6500AA

AF:

0.00529

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000577

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCDC174-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 07, 2020

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.0088

T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.8

.;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.5

.;N;D

REVEL

Benign

0.25

Sift

Uncertain

0.029

.;D;T

Sift4G

Benign

0.15

T;D;D

Polyphen

1.0

.;D;.

Vest4

0.46

MVP

0.81

MPC

0.091

ClinPred

0.052

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.25

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.010

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