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GeneBe

16-56434401-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007006.3(NUDT21):c.592T>C(p.Leu198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,613,814 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

NUDT21
NM_007006.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.48
Variant links:
Genes affected
NUDT21 (HGNC:13870): (nudix hydrolase 21) The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. This gene encodes the 25kD subunit of the protein complex, which is composed of four polypeptides. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-56434401-A-G is Benign according to our data. Variant chr16-56434401-A-G is described in ClinVar as [Benign]. Clinvar id is 730270.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.48 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd4 at 126 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NUDT21NM_007006.3 linkuse as main transcriptc.592T>C p.Leu198= synonymous_variant 6/7 ENST00000300291.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NUDT21ENST00000300291.10 linkuse as main transcriptc.592T>C p.Leu198= synonymous_variant 6/71 NM_007006.3 P1
NUDT21ENST00000566340.5 linkuse as main transcriptc.394T>C p.Leu132= synonymous_variant 6/63
NUDT21ENST00000563860.1 linkuse as main transcriptn.504T>C non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000828
AC:
126
AN:
152240
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00246
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
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:
0.00239
GnomAD3 exomes
AF:
0.000207
AC:
52
AN:
251408
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.00265
Gnomad AMR exome
AF:
0.000174
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:
0.00000879
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000103
AC:
150
AN:
1461456
Hom.:
1
Cov.:
30
AF XY:
0.0000963
AC XY:
70
AN XY:
727044
show subpopulations
Gnomad4 AFR exome
AF:
0.00284
Gnomad4 AMR exome
AF:
0.000313
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:
0.00000360
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000827
AC:
126
AN:
152358
Hom.:
1
Cov.:
32
AF XY:
0.000698
AC XY:
52
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00245
Gnomad4 AMR
AF:
0.00118
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:
0.00237
Alfa
AF:
0.000392
Hom.:
0
Bravo
AF:
0.000960
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
6.8
Dann
Benign
0.78
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1

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.

Other links and lift over

dbSNP: rs150239589; hg19: chr16-56468313; API