chr3-14670514-G-A

Variant names:

• chr3-14670514-G-A
• rs10510430
• NM_016474.5:c.1106-382G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016474.5(CCDC174):​c.1106-382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0346 in 152,300 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.035 (209 hom., cov: 33)
• Consequence: CCDC174 NM_016474.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016474.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC174	NM_016474.5	MANE Select	c.1106-382G>A		intron	N/A	NP_057558.3
	CCDC174	NM_001410719.1		c.878-382G>A		intron	N/A	NP_001397648.1
	CCDC174	NR_135523.2		n.1086-382G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC174	ENST00000383794.7	TSL:1 MANE Select	c.1106-382G>A		intron	N/A	ENSP00000373304.3
	CCDC174	ENST00000303688.8	TSL:5	c.878-382G>A		intron	N/A	ENSP00000302344.7
	CCDC174	ENST00000476763.1	TSL:2	n.334-382G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0345 AC: 5257 AN: 152182 Hom.: 206 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00789

Gnomad OTH AF: 0.0268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0346 AC: 5269 AN: 152300 Hom.: 209 Cov.: 33 AF XY: 0.0331 AC XY: 2466 AN XY: 74468

African (AFR) AF: 0.101 AC: 4204 AN: 41548

American (AMR) AF: 0.0199 AC: 304 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 106 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00249 AC: 12 AN: 4824

European-Finnish (FIN) AF: 0.00339 AC: 36 AN: 10624

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00789 AC: 537 AN: 68026

Other (OTH) AF: 0.0265 AC: 56 AN: 2114

Alfa AF: 0.0284 Hom.: 24

Bravo AF: 0.0393

Asia WGS AF: 0.00866 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.6
DANN	Benign	0.85
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10510430; hg19: chr3-14712021;