dbSNP rs371366392: CCDC174:p.Thr47Asn (chr3-14654523-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016474.5(CCDC174):c.140C>A(p.Thr47Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,312,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T47S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

CCDC174
NM_016474.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.446

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06262234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC174	NM_016474.5 link	c.140C>A	p.Thr47Asn	missense_variant	Exon 2 of 11	ENST00000383794.7	NP_057558.3	Q6PII3
CCDC174	NM_001410719.1 link	c.140C>A	p.Thr47Asn	missense_variant	Exon 2 of 9		NP_001397648.1
CCDC174	XM_017006555.3 link	c.140C>A	p.Thr47Asn	missense_variant	Exon 2 of 8		XP_016862044.1
CCDC174	NR_135523.2 link	n.215C>A		non_coding_transcript_exon_variant	Exon 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC174	ENST00000383794.7 link	c.140C>A	p.Thr47Asn	missense_variant	Exon 2 of 11	1	NM_016474.5	ENSP00000373304.3	Q6PII3
CCDC174	ENST00000465759.1 link	n.204C>A		non_coding_transcript_exon_variant	Exon 2 of 7	1
CCDC174	ENST00000303688.8 link	c.140C>A	p.Thr47Asn	missense_variant	Exon 2 of 9	5		ENSP00000302344.7	A0A0B4J1R8
CCDC174	ENST00000463438.5 link	n.213C>A		non_coding_transcript_exon_variant	Exon 2 of 5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.62e-7

AC:

AN:

1312528

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

659932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.053

Sift

Benign

0.47

T;T

Sift4G

Benign

0.42

T;T

Polyphen

0.14

B;.

Vest4

0.27

MutPred

0.17

Gain of glycosylation at T46 (P = 0.0155);Gain of glycosylation at T46 (P = 0.0155);

MVP

0.19

MPC

0.10

ClinPred

0.053

GERP RS

3.6

Varity_R

0.032

gMVP

0.18

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over