chr13-102730054-A-G

Position:

• chr13-102730054-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001146197.3(CCDC168):​c.20643T>C​(p.His6881=) 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 1,551,488 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (3 hom.)
• Consequence: CCDC168 NM_001146197.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.12

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-102730054-A-G is Benign according to our data. Variant chr13-102730054-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 916408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.12 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC168	NM_001146197.3	c.20643T>C	p.His6881=	synonymous_variant	4/4	ENST00000322527.4
CCDC168	XM_011521106.2	c.20523T>C	p.His6841=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC168	ENST00000322527.4	c.20643T>C	p.His6881=	synonymous_variant	4/4	3	NM_001146197.3	P1

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.000339 AC: 53 AN: 156426 Hom.: 0 AF XY: 0.000326 AC XY: 27 AN XY: 82764

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.000284

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000612

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000426 AC: 596 AN: 1399178 Hom.: 3 Cov.: 33 AF XY: 0.000456 AC XY: 315 AN XY: 690114

Gnomad4 AFR exome AF: 0.000253

Gnomad4 AMR exome AF: 0.000308

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.0000407

Gnomad4 NFE exome AF: 0.000443

Gnomad4 OTH exome AF: 0.000724

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74472

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.000442 Hom.: 0

Bravo AF: 0.000453

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.69

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: rs139179962; hg19: chr13-103382404;