13-102729662-T-G

Position:

• chr13-102729662-T-G

Variant summary

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

The NM_001146197.3(CCDC168):​c.21035A>C​(p.Asn7012Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/14 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)
• Consequence: CCDC168 NM_001146197.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.838

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=0.09482345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC168	NM_001146197.3	c.21035A>C	p.Asn7012Thr	missense_variant	4/4	ENST00000322527.4
CCDC168	XM_011521106.2	c.20915A>C	p.Asn6972Thr	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC168	ENST00000322527.4	c.21035A>C	p.Asn7012Thr	missense_variant	4/4	3	NM_001146197.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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, 2023

The c.21035A>C (p.N7012T) alteration is located in exon 4 (coding exon 4) of the CCDC168 gene. This alteration results from a A to C substitution at nucleotide position 21035, causing the asparagine (N) at amino acid position 7012 to be replaced by a threonine (T). 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	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.5
DANN	Benign	0.89
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
REVEL	Benign	0.034
Sift4G	Pathogenic	0.0	D
Vest4		0.23
MVP		0.014
ClinPred		0.33	T
GERP RS		-8.0
gMVP		0.011

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: chr13-103382012;