rs147383777

Variant names:

• chr3-180605796-T-C
• rs147383777
• NM_133462.4:c.888T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_133462.4(TTC14):​c.888T>C​(p.Ser296Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,570,098 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0025 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (2 hom.)
• Consequence: TTC14 NM_133462.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.720
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-180605796-T-C is Benign according to our data. Variant chr3-180605796-T-C is described in ClinVar as Benign. ClinVar VariationId is 3050662.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.72 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.888T>C	p.Ser296Ser	synonymous	Exon 7 of 12	NP_597719.1	Q96N46-1
	TTC14	NM_001288582.2		c.888T>C	p.Ser296Ser	synonymous	Exon 7 of 13	NP_001275511.1	Q96N46-2
	TTC14	NM_001042601.3		c.888T>C	p.Ser296Ser	synonymous	Exon 7 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.888T>C	p.Ser296Ser	synonymous	Exon 7 of 12	ENSP00000296015.4	Q96N46-1
	TTC14	ENST00000382584.8	TSL:1	c.888T>C	p.Ser296Ser	synonymous	Exon 7 of 13	ENSP00000372027.4	Q96N46-2
	TTC14	ENST00000412756.6	TSL:1	c.888T>C	p.Ser296Ser	synonymous	Exon 7 of 10	ENSP00000413743.2	Q96N46-3

Frequencies

GnomAD3 genomes AF: 0.00253 AC: 385 AN: 152226 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.000714 AC: 148 AN: 207376 AF XY: 0.000493

Gnomad AFR exome AF: 0.00975

Gnomad AMR exome AF: 0.000375

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000995

Gnomad OTH exome AF: 0.000413

GnomAD4 exome AF: 0.000195 AC: 277 AN: 1417754 Hom.: 2 Cov.: 30 AF XY: 0.000176 AC XY: 124 AN XY: 705442

African (AFR) AF: 0.00714 AC: 211 AN: 29570

American (AMR) AF: 0.000502 AC: 15 AN: 29874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24256

East Asian (EAS) AF: 0.00 AC: 0 AN: 37872

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1099832

Other (OTH) AF: 0.000787 AC: 46 AN: 58462

GnomAD4 genome AF: 0.00253 AC: 386 AN: 152344 Hom.: 5 Cov.: 33 AF XY: 0.00240 AC XY: 179 AN XY: 74504

African (AFR) AF: 0.00859 AC: 357 AN: 41584

American (AMR) AF: 0.00137 AC: 21 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00118 Hom.: 0

Bravo AF: 0.00312

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.51
CADD	Benign	8.4
DANN	Benign	0.82
PhyloP100		0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs147383777; hg19: chr3-180323584;