Genetic Variant NT5DC1:p.Pro31Ser (chr6-116101021-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152729.3(NT5DC1):c.91C>T(p.Pro31Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,440,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P31R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

NT5DC1
NM_152729.3 missense, splice_region

Scores

Splicing: ADA: 0.001001

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.174

Publications

0 publications found

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]

NT5DC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030340731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3 link	c.91C>T	p.Pro31Ser	missense_variant, splice_region_variant	Exon 1 of 12	ENST00000319550.9	NP_689942.2	Q5TFE4-1Q9H2R1
NT5DC1	XM_006715378.4 link	c.91C>T	p.Pro31Ser	missense_variant, splice_region_variant	Exon 1 of 10		XP_006715441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5DC1	ENST00000319550.9 link	c.91C>T	p.Pro31Ser	missense_variant, splice_region_variant	Exon 1 of 12	1	NM_152729.3	ENSP00000326858.3		Q5TFE4-1
NT5DC1	ENST00000419791.3 link	c.91C>T	p.Pro31Ser	missense_variant, splice_region_variant	Exon 1 of 7	3		ENSP00000393578.1		Q5QPD0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1440964

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30738

American (AMR)

AF:

0.00

AC:

AN:

43432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25436

East Asian (EAS)

AF:

0.00

AC:

AN:

37400

South Asian (SAS)

AF:

0.0000355

AC:

AN:

84442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102410

Other (OTH)

AF:

0.00

AC:

AN:

59648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.91C>T (p.P31S) alteration is located in exon 1 (coding exon 1) of the NT5DC1 gene. This alteration results from a C to T substitution at nucleotide position 91, causing the proline (P) at amino acid position 31 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

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0044

T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.32

N;.

PhyloP100

0.17

PrimateAI

Benign

0.36

PROVEAN

Benign

0.58

N;N

REVEL

Benign

0.028

Sift

Benign

0.58

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0030

B;.

Vest4

0.19

MutPred

0.46

Gain of helix (P = 0.132);Gain of helix (P = 0.132);

MVP

0.15

MPC

0.13

ClinPred

0.061

GERP RS

0.27

PromoterAI

0.090

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.57

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0010

dbscSNV1_RF

Benign

0.066

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

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6-116101021-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over