Variant 17-42799074-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_173478.3(CNTD1):c.7G>A(p.Gly3Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,613,756 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 4 hom. )

Consequence

CNTD1
NM_173478.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.175

Variant links:

Genes affected

CNTD1 (HGNC:26847): (cyclin N-terminal domain containing 1) Predicted to be involved in reciprocal meiotic recombination. Predicted to act upstream of or within spermatogenesis. Predicted to be active in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

CNTD1 links:

CNTD1 (HGNC:):

CNTD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010126799).

BP6

Variant 17-42799074-G-A is Benign according to our data. Variant chr17-42799074-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2389299.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTD1	NM_173478.3 linkuse as main transcript	c.7G>A	p.Gly3Arg	missense_variant	1/7	ENST00000588408.6	NP_775749.2	Q8N815-1
CNTD1	NM_001330222.2 linkuse as main transcript	c.-81+56G>A		intron_variant			NP_001317151.1	Q8N815B4DXR6
CNTD1	XM_024450569.2 linkuse as main transcript	c.13+244G>A		intron_variant			XP_024306337.1
CNTD1	XM_011524311.3 linkuse as main transcript	c.-5+244G>A		intron_variant			XP_011522613.1	B4DXR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTD1	ENST00000588408.6 linkuse as main transcript	c.7G>A	p.Gly3Arg	missense_variant	1/7	1	NM_173478.3	ENSP00000465204.1		Q8N815-1

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00151

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000722

AC:

181

AN:

250648

Hom.:

AF XY:

0.000752

AC XY:

102

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.000371

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00140

AC:

2044

AN:

1461572

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

1018

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000789

AC:

120

AN:

152184

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.000771

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000684

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.3

DANN

Benign

0.85

DEOGEN2

Benign

0.0036

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.48

M_CAP

Benign

0.0069

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.92

PrimateAI

Benign

0.34

Sift4G

Benign

0.70

Polyphen

0.014

Vest4

0.083

MutPred

0.15

Gain of solvent accessibility (P = 0.0674);

MVP

0.15

MPC

0.25

ClinPred

0.0022

GERP RS

-2.5

Varity_R

0.062

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

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