13-102729996-C-T

Position:

• chr13-102729996-C-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.20701G>A​(p.Glu6901Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 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: 0.0000014 (0 hom.)
• Consequence: CCDC168 NM_001146197.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

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=0.11135161).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC168	NM_001146197.3	c.20701G>A	p.Glu6901Lys	missense_variant	4/4	ENST00000322527.4	NP_001139669.1
CCDC168	XM_011521106.2	c.20581G>A	p.Glu6861Lys	missense_variant	5/5		XP_011519408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC168	ENST00000322527.4	c.20701G>A	p.Glu6901Lys	missense_variant	4/4	3	NM_001146197.3	ENSP00000320232.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399490 Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1 AN XY: 690240

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: 0.00000185

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.20701G>A (p.E6901K) alteration is located in exon 4 (coding exon 4) of the CCDC168 gene. This alteration results from a G to A substitution at nucleotide position 20701, causing the glutamic acid (E) at amino acid position 6901 to be replaced by a lysine (K). 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	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	1.0
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.052	N
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.31	T
REVEL	Benign	0.031
Sift4G	Uncertain	0.0060	D
Vest4		0.16
MVP		0.067
ClinPred		0.73	D
GERP RS		3.4
gMVP		0.033

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: rs1273267409; hg19: chr13-103382346;