Variant 17-42809494-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173478.3(CNTD1):c.952G>A(p.Ala318Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,614,052 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000080 ( 1 hom. )

Consequence

CNTD1
NM_173478.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02781704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CNTD1	NM_173478.3 linkuse as main transcript	c.952G>A	p.Ala318Thr	missense_variant	7/7	ENST00000588408.6
CNTD1	NM_001330222.2 linkuse as main transcript	c.703G>A	p.Ala235Thr	missense_variant	7/7
CNTD1	XM_011524311.3 linkuse as main transcript	c.703G>A	p.Ala235Thr	missense_variant	6/6
CNTD1	XM_024450569.2 linkuse as main transcript	c.*77G>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTD1	ENST00000588408.6 linkuse as main transcript	c.952G>A	p.Ala318Thr	missense_variant	7/7	1	NM_173478.3	P1	Q8N815-1
CNTD1	ENST00000315066.5 linkuse as main transcript	n.564G>A		non_coding_transcript_exon_variant	5/5	1
CNTD1	ENST00000588527.5 linkuse as main transcript	c.703G>A	p.Ala235Thr	missense_variant	7/7	2
CNTD1	ENST00000586652.1 linkuse as main transcript	c.*77G>A		3_prime_UTR_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000255

AC:

AN:

251422

Hom.:

AF XY:

0.000213

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00147

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:

0.000106

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000800

AC:

117

AN:

1461856

Hom.:

Cov.:

AF XY:

0.0000894

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000378

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000105

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000169

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jun 03, 2022

The c.952G>A (p.A318T) alteration is located in exon 7 (coding exon 7) of the CNTD1 gene. This alteration results from a G to A substitution at nucleotide position 952, causing the alanine (A) at amino acid position 318 to be replaced by a threonine (T). 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

0.090

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.61

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0025

T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.059

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.82

N;N

PrimateAI

Benign

0.30

Sift4G

Benign

0.13

T;T

Polyphen

0.0030

B;.

Vest4

0.13

MutPred

0.33

Gain of glycosylation at A318 (P = 0.0087);.;

MVP

0.57

MPC

0.22

ClinPred

0.015

GERP RS

4.0

Varity_R

0.062

gMVP

0.23

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

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