6-151573432-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_025059.4(CCDC170):c.1033G>A(p.Glu345Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00832 in 1,614,146 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0053 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (71 hom.)
• Consequence: CCDC170 NM_025059.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 3.86

Genes affected

CCDC170 (HGNC:21177): (coiled-coil domain containing 170) The function of this gene and its encoded protein is not known. Several genome-wide association studies have implicated the region around this gene to be involved in breast cancer and bone mineral density, but no link to this specific gene has been found. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007223755).
• BP6: Variant 6-151573432-G-A is Benign according to our data. Variant chr6-151573432-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 993917.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC170	NM_025059.4	c.1033G>A	p.Glu345Lys	missense_variant	6/11	ENST00000239374.8
CCDC170	XM_011536147.3	c.1051G>A	p.Glu351Lys	missense_variant	6/11
CCDC170	XM_011536148.3	c.1051G>A	p.Glu351Lys	missense_variant	6/10
CCDC170	XM_047419372.1	c.1033G>A	p.Glu345Lys	missense_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC170	ENST00000239374.8	c.1033G>A	p.Glu345Lys	missense_variant	6/11	1	NM_025059.4	P1

Frequencies

GnomAD3 genomes AF: 0.00526 AC: 800 AN: 152174 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00920

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00530 AC: 1320 AN: 249272 Hom.: 1 AF XY: 0.00525 AC XY: 710 AN XY: 135234

Gnomad AFR exome AF: 0.00181

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00183

Gnomad FIN exome AF: 0.00436

Gnomad NFE exome AF: 0.00933

Gnomad OTH exome AF: 0.00430

GnomAD4 exome AF: 0.00864 AC: 12626 AN: 1461854 Hom.: 71 Cov.: 35 AF XY: 0.00843 AC XY: 6130 AN XY: 727236

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00150

Gnomad4 FIN exome AF: 0.00475

Gnomad4 NFE exome AF: 0.0105

Gnomad4 OTH exome AF: 0.00694

GnomAD4 genome AF: 0.00526 AC: 801 AN: 152292 Hom.: 3 Cov.: 32 AF XY: 0.00492 AC XY: 366 AN XY: 74460

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00920

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00807 Hom.: 7

Bravo AF: 0.00488

TwinsUK AF: 0.0138 AC: 51

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.00154 AC: 6

ESP6500EA AF: 0.00765 AC: 63

ExAC AF: 0.00543 AC: 656

Asia WGS AF: 0.000577 AC: 3 AN: 3478

EpiCase AF: 0.00823

EpiControl AF: 0.00753

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	May 05, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	CCDC170: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.0072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.097
Sift	Benign	0.079	T
Sift4G	Benign	0.22	T
Polyphen		0.61	P
Vest4		0.34
MVP		0.20
MPC		0.28
ClinPred		0.029	T
GERP RS		4.7
Varity_R		0.26
gMVP		0.57

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: rs55868409; hg19: chr6-151894567;