Variant 10-80339129-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001269053.2(DYDC1):c.367C>A(p.Leu123Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DYDC1
NM_001269053.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.558

Variant links:

Genes affected

DYDC1 (HGNC:23460): (DPY30 domain containing 1) This gene encodes a member of a family of proteins that contains a DPY30 domain. The encoded protein is involved in acrosome formation during spermatid development. This gene locus overlaps with a closely related gene on the opposite strand. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

DYDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03302309).

BP6

Variant 10-80339129-G-T is Benign according to our data. Variant chr10-80339129-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2535884.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYDC1	NM_001269053.2 linkuse as main transcript	c.367C>A	p.Leu123Ile	missense_variant	5/7	ENST00000372202.6	NP_001255982.1	Q8WWB3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DYDC1	ENST00000372202.6 linkuse as main transcript	c.367C>A	p.Leu123Ile	missense_variant	5/7	3	NM_001269053.2	ENSP00000361276.1	Q8WWB3-1
DYDC1	ENST00000372204.7 linkuse as main transcript	c.367C>A	p.Leu123Ile	missense_variant	6/8	1		ENSP00000361278.3	Q8WWB3-1
DYDC1	ENST00000421924.6 linkuse as main transcript	c.367C>A	p.Leu123Ile	missense_variant	4/6	1		ENSP00000402890.3	Q8WWB3-1
DYDC1	ENST00000454362.5 linkuse as main transcript	c.367C>A	p.Leu123Ile	missense_variant	5/6	2		ENSP00000414798.1	X1WI33

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1212908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

606186

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Apr 11, 2023

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

0.059

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.024

DANN

Benign

0.39

DEOGEN2

Benign

0.016

T;T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.30

.;T;.;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.68

N;N;N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.54

N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.47

T;T;T;T

Sift4G

Benign

0.70

T;T;T;.

Polyphen

0.0

B;B;B;.

Vest4

0.096

MutPred

0.22

Gain of MoRF binding (P = 0.1015);Gain of MoRF binding (P = 0.1015);Gain of MoRF binding (P = 0.1015);Gain of MoRF binding (P = 0.1015);

MVP

0.067

MPC

0.10

ClinPred

0.28

GERP RS

-4.6

Varity_R

0.038

gMVP

0.032

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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