13-102729956-G-A

Variant names:

• chr13-102729956-G-A
• NM_001146197.3:c.20741C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146197.3(CCDC168):​c.20741C>T​(p.Ser6914Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CCDC168 NM_001146197.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

Genes affected

CCDC168 (HGNC:26851): (coiled-coil domain containing 168)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19031808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC168	NM_001146197.3	c.20741C>T	p.Ser6914Phe	missense_variant	Exon 4 of 4	ENST00000322527.4	NP_001139669.1
CCDC168	XM_011521106.2	c.20621C>T	p.Ser6874Phe	missense_variant	Exon 5 of 5		XP_011519408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC168	ENST00000322527.4	c.20741C>T	p.Ser6914Phe	missense_variant	Exon 4 of 4	3	NM_001146197.3	ENSP00000320232.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399646 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 690314

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20741C>T (p.S6914F) alteration is located in exon 4 (coding exon 4) of the CCDC168 gene. This alteration results from a C to T substitution at nucleotide position 20741, causing the serine (S) at amino acid position 6914 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.095
FATHMM_MKL	Benign	0.28	N
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.32	T
REVEL	Benign	0.085
Sift4G	Uncertain	0.0020	D
Vest4		0.12
MVP		0.29
ClinPred		0.77	D
GERP RS		4.2
gMVP		0.015

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-103382306;