rs11709673

Variant names:

• chr3-14671799-A-G
• rs11709673
• NM_016474.5:c.*605A>G

Variant summary

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

The NM_016474.5(CCDC174):​c.*605A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,542 control chromosomes in the GnomAD database, including 8,447 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 0.33 (8436 hom., cov: 33)
  • Exomes 𝑓: 0.25 (11 hom.)
• Consequence: CCDC174 NM_016474.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.886
• Publications: 11 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.379 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.*605A>G		3_prime_UTR	Exon 11 of 11	NP_057558.3
	CCDC174	NM_001410719.1		c.*605A>G		3_prime_UTR	Exon 9 of 9	NP_001397648.1	A0A0B4J1R8
	CCDC174	NR_135523.2		n.1989A>G		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC174	ENST00000383794.7	TSL:1 MANE Select	c.*605A>G		3_prime_UTR	Exon 11 of 11	ENSP00000373304.3	Q6PII3
	CCDC174	ENST00000303688.8	TSL:5	c.*605A>G		3_prime_UTR	Exon 9 of 9	ENSP00000302344.7	A0A0B4J1R8

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50184 AN: 152046 Hom.: 8425 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.246 AC: 93 AN: 378 Hom.: 11 Cov.: 0 AF XY: 0.277 AC XY: 57 AN XY: 206

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.292 AC: 7 AN: 24

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.167 AC: 1 AN: 6

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.242 AC: 76 AN: 314

Other (OTH) AF: 0.208 AC: 5 AN: 24

GnomAD4 genome AF: 0.330 AC: 50230 AN: 152164 Hom.: 8436 Cov.: 33 AF XY: 0.330 AC XY: 24580 AN XY: 74400

African (AFR) AF: 0.298 AC: 12373 AN: 41488

American (AMR) AF: 0.387 AC: 5918 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3468

East Asian (EAS) AF: 0.245 AC: 1270 AN: 5182

South Asian (SAS) AF: 0.248 AC: 1196 AN: 4826

European-Finnish (FIN) AF: 0.424 AC: 4489 AN: 10594

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22799 AN: 67996

Other (OTH) AF: 0.347 AC: 734 AN: 2114

Alfa AF: 0.329 Hom.: 23557

Bravo AF: 0.331

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.95
DANN	Benign	0.34
PhyloP100		-0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs11709673; hg19: chr3-14713306;