chr6-116108400-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152729.3(NT5DC1):​c.222C>A​(p.Asn74Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NT5DC1
NM_152729.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.775
Variant links:
Genes affected
NT5DC1 (HGNC:21556): (5'-nucleotidase domain containing 1) While the exact function of the protein encoded by this gene is not known, it belongs to the 5'(3')-deoxyribonucleotidase family. [provided by RefSeq, May 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33492732).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NT5DC1NM_152729.3 linkuse as main transcriptc.222C>A p.Asn74Lys missense_variant 3/12 ENST00000319550.9
NT5DC1XM_006715378.4 linkuse as main transcriptc.222C>A p.Asn74Lys missense_variant 3/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NT5DC1ENST00000319550.9 linkuse as main transcriptc.222C>A p.Asn74Lys missense_variant 3/121 NM_152729.3 P1Q5TFE4-1
NT5DC1ENST00000419791.3 linkuse as main transcriptc.222C>A p.Asn74Lys missense_variant 3/73

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1457460
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
725460
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
Cov.:
32

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 submitterclinical testingAmbry GeneticsJan 03, 2024The c.222C>A (p.N74K) alteration is located in exon 3 (coding exon 3) of the NT5DC1 gene. This alteration results from a C to A substitution at nucleotide position 222, causing the asparagine (N) at amino acid position 74 to be replaced by a lysine (K). 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
Uncertain
0.52
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T;T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.85
T;T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M;.
MutationTaster
Benign
0.98
D
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.6
D;D
REVEL
Benign
0.16
Sift
Uncertain
0.016
D;D
Sift4G
Uncertain
0.016
D;D
Polyphen
0.035
B;.
Vest4
0.55
MutPred
0.55
Gain of ubiquitination at N74 (P = 0.0258);Gain of ubiquitination at N74 (P = 0.0258);
MVP
0.43
MPC
0.18
ClinPred
0.93
D
GERP RS
2.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.31
gMVP
0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-116429563; API