chr6-116115750-G-T

Variant names:

• chr6-116115750-G-T
• rs200158849
• NM_152729.3:c.424G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_152729.3(NT5DC1):​c.424G>T​(p.Val142Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000993 in 1,590,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V142M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: NT5DC1 NM_152729.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3	c.424G>T	p.Val142Leu	missense_variant	Exon 5 of 12	ENST00000319550.9	NP_689942.2
NT5DC1	XM_006715378.4	c.424G>T	p.Val142Leu	missense_variant	Exon 5 of 10		XP_006715441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5DC1	ENST00000319550.9	c.424G>T	p.Val142Leu	missense_variant	Exon 5 of 12	1	NM_152729.3	ENSP00000326858.3
NT5DC1	ENST00000419791.3	c.424G>T	p.Val142Leu	missense_variant	Exon 5 of 7	3		ENSP00000393578.1
NT5DC1	ENST00000417846.2	n.165G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000104 AC: 26 AN: 251162 AF XY: 0.000125

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000104 AC: 149 AN: 1438328 Hom.: 0 Cov.: 24 AF XY: 0.000109 AC XY: 78 AN XY: 717060

African (AFR) AF: 0.00 AC: 0 AN: 33050

American (AMR) AF: 0.0000672 AC: 3 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25948

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.00 AC: 0 AN: 85696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.000130 AC: 142 AN: 1090786

Other (OTH) AF: 0.0000671 AC: 4 AN: 59632

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74482

African (AFR) AF: 0.0000241 AC: 1 AN: 41566

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000509 Hom.: 0

Bravo AF: 0.0000491

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PhyloP100		2.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.067
Sift	Benign	0.066	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.15	B;.
Vest4		0.29
MutPred		0.61		Loss of MoRF binding (P = 0.3569);Loss of MoRF binding (P = 0.3569);
MVP		0.18
MPC		0.13
ClinPred		0.038	T
GERP RS		2.4
Varity_R		0.067
gMVP		0.67
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.69		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.69		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200158849; hg19: chr6-116436913;