3-180606262-C-T

Variant names:

• chr3-180606262-C-T
• rs201415238
• NM_133462.4:c.939C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_133462.4(TTC14):​c.939C>T​(p.Ile313Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: TTC14 NM_133462.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.688
• Publications: 1 publications found

Genes affected

TTC14 (HGNC:24697): (tetratricopeptide repeat domain 14) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CCDC39 (HGNC:25244): (coiled-coil domain 39 molecular ruler complex subunit) The protein encoded by this gene is involved in the motility of cilia and flagella. The encoded protein is essential for the assembly of dynein regulatory and inner dynein arm complexes, which regulate ciliary beat. Defects in this gene are a cause of primary ciliary dyskinesia type 14 (CILD14). [provided by RefSeq, Jul 2011]

CCDC39 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 14

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 3-180606262-C-T is Benign according to our data. Variant chr3-180606262-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3048566.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.688 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133462.4. 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
	TTC14	NM_133462.4	MANE Select	c.939C>T	p.Ile313Ile	synonymous	Exon 8 of 12	NP_597719.1	Q96N46-1
	TTC14	NM_001288582.2		c.939C>T	p.Ile313Ile	synonymous	Exon 8 of 13	NP_001275511.1	Q96N46-2
	TTC14	NM_001042601.3		c.939C>T	p.Ile313Ile	synonymous	Exon 8 of 10	NP_001036066.1	Q96N46-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC14	ENST00000296015.9	TSL:1 MANE Select	c.939C>T	p.Ile313Ile	synonymous	Exon 8 of 12	ENSP00000296015.4	Q96N46-1
	TTC14	ENST00000382584.8	TSL:1	c.939C>T	p.Ile313Ile	synonymous	Exon 8 of 13	ENSP00000372027.4	Q96N46-2
	TTC14	ENST00000412756.6	TSL:1	c.939C>T	p.Ile313Ile	synonymous	Exon 8 of 10	ENSP00000413743.2	Q96N46-3

Frequencies

GnomAD3 genomes AF: 0.000362 AC: 55 AN: 152064 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000757

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000199 AC: 50 AN: 251212 AF XY: 0.000214

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000107 AC: 157 AN: 1461620 Hom.: 0 Cov.: 31 AF XY: 0.0000921 AC XY: 67 AN XY: 727120

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.000380 AC: 17 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86228

European-Finnish (FIN) AF: 0.00112 AC: 60 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111890

Other (OTH) AF: 0.000215 AC: 13 AN: 60372

GnomAD4 genome AF: 0.000361 AC: 55 AN: 152182 Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27 AN XY: 74402

African (AFR) AF: 0.0000482 AC: 2 AN: 41520

American (AMR) AF: 0.00229 AC: 35 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000757 AC: 8 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68012

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000575 Hom.: 0

Bravo AF: 0.000529

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TTC14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs201415238; hg19: chr3-180324050; COSMIC: COSV56010835; COSMIC: COSV56010835;