Variant 8-109289895-G-A 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_032869.4(NUDCD1):c.679C>T(p.Arg227Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000765 in 1,529,272 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000079 ( 1 hom. )

Consequence

NUDCD1
NM_032869.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

NUDCD1 (HGNC:24306): (NudC domain containing 1) Predicted to be involved in immune system process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

NUDCD1 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=0.06029755).

BP6

Variant 8-109289895-G-A is Benign according to our data. Variant chr8-109289895-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2596824.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NUDCD1	NM_032869.4 linkuse as main transcript	c.679C>T	p.Arg227Cys	missense_variant	5/10	ENST00000239690.9
NUDCD1	NM_001128211.2 linkuse as main transcript	c.592C>T	p.Arg198Cys	missense_variant	5/10
NUDCD1	XM_047422330.1 linkuse as main transcript	c.418C>T	p.Arg140Cys	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDCD1	ENST00000239690.9 linkuse as main transcript	c.679C>T	p.Arg227Cys	missense_variant	5/10	1	NM_032869.4	P1	Q96RS6-1

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000106

AC:

AN:

189262

Hom.:

AF XY:

0.000115

AC XY:

AN XY:

104264

show subpopulations

Gnomad AFR exome

AF:

0.0000859

Gnomad AMR exome

AF:

0.0000517

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000796

Gnomad SAS exome

AF:

0.000279

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000325

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000791

AC:

109

AN:

1377348

Hom.:

Cov.:

AF XY:

0.0000905

AC XY:

AN XY:

684860

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000337

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00253

Gnomad4 SAS exome

AF:

0.000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000112

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151924

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000277

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3474

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

Jun 16, 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

0.080

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.043

Sift

Benign

0.18

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0010

B;B

Vest4

0.18

MutPred

0.47

Loss of MoRF binding (P = 0.004);.;

MVP

0.33

MPC

0.15

ClinPred

0.051

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.062

gMVP

0.40

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