Genetic Variant NT5DC1:p.Asp157Gly (chr6-116117886-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152729.3(NT5DC1):c.470A>G(p.Asp157Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000491 in 1,426,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

NT5DC1
NM_152729.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3 link	c.470A>G	p.Asp157Gly	missense_variant	Exon 6 of 12	ENST00000319550.9	NP_689942.2	Q5TFE4-1Q9H2R1
NT5DC1	XM_006715378.4 link	c.470A>G	p.Asp157Gly	missense_variant	Exon 6 of 10		XP_006715441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NT5DC1	ENST00000319550.9 link	c.470A>G	p.Asp157Gly	missense_variant	Exon 6 of 12	1	NM_152729.3	ENSP00000326858.3	Q5TFE4-1
NT5DC1	ENST00000419791.3 link	c.470A>G	p.Asp157Gly	missense_variant	Exon 6 of 7	3		ENSP00000393578.1	Q5QPD0
NT5DC1	ENST00000417846.2 link	n.211A>G		non_coding_transcript_exon_variant	Exon 3 of 3	3
NT5DC1	ENST00000460749.1 link	n.-35A>G		upstream_gene_variant		5		ENSP00000433238.1	H0YDA5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

247502

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000491

AC:

AN:

1426206

Hom.:

Cov.:

AF XY:

0.00000844

AC XY:

AN XY:

711218

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32756

American (AMR)

AF:

0.00

AC:

AN:

43946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25878

East Asian (EAS)

AF:

0.00

AC:

AN:

39456

South Asian (SAS)

AF:

0.00

AC:

AN:

84216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.00000647

AC:

AN:

1081716

Other (OTH)

AF:

0.00

AC:

AN:

59232

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000752), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.354

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 29, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.470A>G (p.D157G) alteration is located in exon 6 (coding exon 6) of the NT5DC1 gene. This alteration results from a A to G substitution at nucleotide position 470, causing the aspartic acid (D) at amino acid position 157 to be replaced by a glycine (G). 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

0.17

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.0

M;.

PhyloP100

5.3

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.22

Sift

Benign

0.035

D;D

Sift4G

Uncertain

0.029

D;D

Polyphen

0.98

D;.

Vest4

0.77

MutPred

0.79

Gain of methylation at K160 (P = 0.036);Gain of methylation at K160 (P = 0.036);

MVP

0.23

MPC

0.24

ClinPred

0.98

GERP RS

5.8

Varity_R

0.25

gMVP

0.78

Mutation Taster

=31/69

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-116117886-A-G

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