Variant 8-109243185-T-G 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_032869.4(NUDCD1):c.1576A>C(p.Met526Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

NUDCD1
NM_032869.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0140250325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NUDCD1	NM_032869.4 linkuse as main transcript	c.1576A>C	p.Met526Leu	missense_variant	10/10	ENST00000239690.9	NP_116258.2
NUDCD1	NM_001128211.2 linkuse as main transcript	c.1489A>C	p.Met497Leu	missense_variant	10/10		NP_001121683.1
NUDCD1	XM_047422330.1 linkuse as main transcript	c.1315A>C	p.Met439Leu	missense_variant	10/10		XP_047278286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUDCD1	ENST00000239690.9 linkuse as main transcript	c.1576A>C	p.Met526Leu	missense_variant	10/10	1	NM_032869.4	ENSP00000239690	P1	Q96RS6-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000175

AC:

AN:

251070

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000201

AC:

294

AN:

1461602

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

149

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000164

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000427

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

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

Aug 12, 2021

The c.1576A>C (p.M526L) alteration is located in exon 10 (coding exon 10) of the NUDCD1 gene. This alteration results from a A to C substitution at nucleotide position 1576, causing the methionine (M) at amino acid position 526 to be replaced by a leucine (L). 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

0.077

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.00089

T;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

N;.

MutationTaster

Benign

0.52

D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.14

Sift

Benign

0.88

T;T

Sift4G

Benign

0.95

T;T

Polyphen

0.0

B;B

Vest4

0.14

MVP

0.13

MPC

0.10

ClinPred

0.0052

GERP RS

2.7

Varity_R

0.060

gMVP

0.096

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