Variant 6-151544572-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025059.4(CCDC170):c.444A>C(p.Gln148His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000887 in 1,609,328 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 3 hom. )

Consequence

CCDC170
NM_025059.4 missense, splice_region

Scores

Splicing: ADA: 0.0008463

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.514

Variant links:

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]

CCDC170 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030461907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC170	NM_025059.4 linkuse as main transcript	c.444A>C	p.Gln148His	missense_variant, splice_region_variant	4/11	ENST00000239374.8
CCDC170	XM_011536147.3 linkuse as main transcript	c.462A>C	p.Gln154His	missense_variant, splice_region_variant	4/11
CCDC170	XM_011536148.3 linkuse as main transcript	c.462A>C	p.Gln154His	missense_variant, splice_region_variant	4/10
CCDC170	XM_047419372.1 linkuse as main transcript	c.444A>C	p.Gln148His	missense_variant, splice_region_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC170	ENST00000239374.8 linkuse as main transcript	c.444A>C	p.Gln148His	missense_variant, splice_region_variant	4/11	1	NM_025059.4	P1
CCDC170	ENST00000544131.1 linkuse as main transcript	n.434A>C		splice_region_variant, non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000435

AC:

108

AN:

248362

Hom.:

AF XY:

0.000467

AC XY:

AN XY:

134826

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.0000873

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000888

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000938

AC:

1367

AN:

1457130

Hom.:

Cov.:

AF XY:

0.000955

AC XY:

692

AN XY:

724262

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000939

Gnomad4 NFE exome

AF:

0.00119

Gnomad4 OTH exome

AF:

0.000598

GnomAD4 genome

AF:

0.000401

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000805

Hom.:

Bravo

AF:

0.000510

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000272

AC:

ESP6500EA

AF:

0.000612

AC:

ExAC

AF:

0.000364

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.444A>C (p.Q148H) alteration is located in exon 4 (coding exon 4) of the CCDC170 gene. This alteration results from a A to C substitution at nucleotide position 444, causing the glutamine (Q) at amino acid position 148 to be replaced by a histidine (H). 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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Benign

0.92

DEOGEN2

Benign

0.0012

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.58

M_CAP

Benign

0.0082

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.82

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

REVEL

Benign

0.035

Sift

Benign

0.099

Sift4G

Benign

0.084

Polyphen

0.066

Vest4

0.28

MutPred

0.077

Gain of ubiquitination at K149 (P = 0.0931);

MVP

0.081

MPC

0.12

ClinPred

0.043

GERP RS

1.9

Varity_R

0.054

gMVP

0.066

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00085

dbscSNV1_RF

Benign

0.092

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over