chr6-116110896-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152729.3(NT5DC1):​c.304G>T​(p.Ala102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,614,036 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 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

NT5DC1
NM_152729.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.685
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1827904).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NT5DC1NM_152729.3 linkuse as main transcriptc.304G>T p.Ala102Ser missense_variant 4/12 ENST00000319550.9
NT5DC1XM_006715378.4 linkuse as main transcriptc.304G>T p.Ala102Ser missense_variant 4/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NT5DC1ENST00000319550.9 linkuse as main transcriptc.304G>T p.Ala102Ser missense_variant 4/121 NM_152729.3 P1Q5TFE4-1
NT5DC1ENST00000419791.3 linkuse as main transcriptc.304G>T p.Ala102Ser missense_variant 4/73
NT5DC1ENST00000417846.2 linkuse as main transcriptn.45G>T non_coding_transcript_exon_variant 1/33

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152232
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000265
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000795
AC:
20
AN:
251438
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
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:
0.000167
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000183
AC:
267
AN:
1461804
Hom.:
0
Cov.:
30
AF XY:
0.000157
AC XY:
114
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.000236
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152232
Hom.:
0
Cov.:
33
AF XY:
0.0000941
AC XY:
7
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000214
Hom.:
0
Bravo
AF:
0.000174
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.000545
EpiControl
AF:
0.000178

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 GeneticsDec 21, 2023The c.304G>T (p.A102S) alteration is located in exon 4 (coding exon 4) of the NT5DC1 gene. This alteration results from a G to T substitution at nucleotide position 304, causing the alanine (A) at amino acid position 102 to be replaced by a serine (S). 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
0.086
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
6.7
DANN
Benign
0.88
DEOGEN2
Benign
0.015
T;T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.057
N
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.97
L;.
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.88
N;N
REVEL
Benign
0.032
Sift
Benign
0.38
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.067
B;.
Vest4
0.18
MVP
0.23
MPC
0.12
ClinPred
0.022
T
GERP RS
0.74
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.033
gMVP
0.53

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: rs200437402; hg19: chr6-116432059; API