13-102730310-A-G

Variant names:

• chr13-102730310-A-G
• rs144153566
• NM_001146197.3:c.20387T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001146197.3(CCDC168):​c.20387T>C​(p.Val6796Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0075 in 1,551,386 control chromosomes in the GnomAD database, including 59 homozygotes. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V6796M) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0054 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (58 hom.)
• Consequence: CCDC168 NM_001146197.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.75

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034114122).
• BP6: Variant 13-102730310-A-G is Benign according to our data. Variant chr13-102730310-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643903.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC168	NM_001146197.3	c.20387T>C	p.Val6796Ala	missense_variant	Exon 4 of 4	ENST00000322527.4	NP_001139669.1
CCDC168	XM_011521106.2	c.20267T>C	p.Val6756Ala	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.20387T>C	p.Val6796Ala	missense_variant	Exon 4 of 4	3	NM_001146197.3	ENSP00000320232.3

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 817 AN: 152182 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00773

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00885

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00448 AC: 696 AN: 155290 Hom.: 5 AF XY: 0.00432 AC XY: 355 AN XY: 82240

Gnomad AFR exome AF: 0.00126

Gnomad AMR exome AF: 0.00405

Gnomad ASJ exome AF: 0.00567

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000264

Gnomad FIN exome AF: 0.000360

Gnomad NFE exome AF: 0.00852

Gnomad OTH exome AF: 0.00435

GnomAD4 exome AF: 0.00773 AC: 10816 AN: 1399086 Hom.: 58 Cov.: 33 AF XY: 0.00753 AC XY: 5194 AN XY: 690052

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00417

Gnomad4 ASJ exome AF: 0.00548

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000240

Gnomad4 FIN exome AF: 0.000611

Gnomad4 NFE exome AF: 0.00930

Gnomad4 OTH exome AF: 0.00662

GnomAD4 genome AF: 0.00536 AC: 816 AN: 152300 Hom.: 1 Cov.: 32 AF XY: 0.00493 AC XY: 367 AN XY: 74466

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.00772

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00883

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00768 Hom.: 6

Bravo AF: 0.00610

TwinsUK AF: 0.0102 AC: 38

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00849 AC: 27

ExAC AF: 0.00324 AC: 80

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CCDC168: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.045	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.28	T
REVEL	Benign	0.038
Sift4G	Uncertain	0.0060	D
Vest4		0.14
MVP		0.040
ClinPred		0.013	T
GERP RS		2.7
gMVP		0.031

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: rs144153566; hg19: chr13-103382660;