rs10510430

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC174	NM_016474.5	c.1106-382G>A		intron_variant	Intron 10 of 10	ENST00000383794.7	NP_057558.3
CCDC174	NM_001410719.1	c.878-382G>A		intron_variant	Intron 8 of 8		NP_001397648.1
CCDC174	NR_135523.2	n.1086-382G>A		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC174	ENST00000383794.7	c.1106-382G>A		intron_variant	Intron 10 of 10	1	NM_016474.5	ENSP00000373304.3
CCDC174	ENST00000303688.8	c.878-382G>A		intron_variant	Intron 8 of 8	5		ENSP00000302344.7
CCDC174	ENST00000476763.1	n.334-382G>A		intron_variant	Intron 2 of 2	2

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

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00789

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0258 Hom.: 17

Bravo AF: 0.0393

Asia WGS AF: 0.00866 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.6
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs10510430; hg19: chr3-14712021;