3-14654469-T-C

Position:

chr3-14654469-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016474.5(CCDC174):c.86T>C(p.Phe29Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000166 in 1,608,082 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

CCDC174
NM_016474.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 6.78

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC174	NM_016474.5 linkuse as main transcript	c.86T>C	p.Phe29Ser	missense_variant	2/11	ENST00000383794.7	NP_057558.3	Q6PII3
CCDC174	NM_001410719.1 linkuse as main transcript	c.86T>C	p.Phe29Ser	missense_variant	2/9		NP_001397648.1
CCDC174	XM_017006555.3 linkuse as main transcript	c.86T>C	p.Phe29Ser	missense_variant	2/8		XP_016862044.1
CCDC174	NR_135523.2 linkuse as main transcript	n.161T>C		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.86T>C	p.Phe29Ser	missense_variant	2/11	1	NM_016474.5	ENSP00000373304.3	Q6PII3
CCDC174	ENST00000465759.1 linkuse as main transcript	n.150T>C		non_coding_transcript_exon_variant	2/7	1
CCDC174	ENST00000303688.8 linkuse as main transcript	c.86T>C	p.Phe29Ser	missense_variant	2/9	5		ENSP00000302344.7	A0A0B4J1R8
CCDC174	ENST00000463438.5 linkuse as main transcript	n.159T>C		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000180

AC:

AN:

244480

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

132720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000301

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:

0.000295

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000161

AC:

235

AN:

1455812

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

126

AN XY:

724220

show subpopulations

Gnomad4 AFR exome

AF:

0.000301

Gnomad4 AMR exome

AF:

0.000297

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000590

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.000266

GnomAD4 genome

AF:

0.000210

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000185

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000494

AC:

ExAC

AF:

0.000182

AC:

EpiCase

AF:

0.000819

EpiControl

AF:

0.000596

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Jun 05, 2023

- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.86T>C (p.F29S) alteration is located in exon 2 (coding exon 2) of the CCDC174 gene. This alteration results from a T to C substitution at nucleotide position 86, causing the phenylalanine (F) at amino acid position 29 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

T;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0090

D;D

Sift4G

Benign

0.13

T;D

Polyphen

1.0

D;.

Vest4

0.89

MVP

0.68

MPC

0.44

ClinPred

0.82

GERP RS

5.4

Varity_R

0.61

gMVP

0.41

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