6-116106274-G-A

Variant names:

• chr6-116106274-G-A
• rs562689401
• NM_152729.3:c.124G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152729.3(NT5DC1):​c.124G>A​(p.Val42Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000058 in 1,585,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: NT5DC1 NM_152729.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.40
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07440767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3	c.124G>A	p.Val42Ile	missense_variant	Exon 2 of 12	ENST00000319550.9	NP_689942.2
NT5DC1	XM_006715378.4	c.124G>A	p.Val42Ile	missense_variant	Exon 2 of 10		XP_006715441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5DC1	ENST00000319550.9	c.124G>A	p.Val42Ile	missense_variant	Exon 2 of 12	1	NM_152729.3	ENSP00000326858.3
NT5DC1	ENST00000419791.3	c.124G>A	p.Val42Ile	missense_variant	Exon 2 of 7	3		ENSP00000393578.1

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 150878 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000482

GnomAD2 exomes AF: 0.0000955 AC: 24 AN: 251352 AF XY: 0.000162

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000606 AC: 87 AN: 1434752 Hom.: 0 Cov.: 27 AF XY: 0.0000825 AC XY: 59 AN XY: 715538

African (AFR) AF: 0.0000304 AC: 1 AN: 32936

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39430

South Asian (SAS) AF: 0.000724 AC: 62 AN: 85684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00115 AC: 6 AN: 5228

European-Non Finnish (NFE) AF: 0.0000138 AC: 15 AN: 1088208

Other (OTH) AF: 0.0000505 AC: 3 AN: 59394

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 150930 Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2 AN XY: 73574

African (AFR) AF: 0.0000243 AC: 1 AN: 41176

American (AMR) AF: 0.00 AC: 0 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.000420 AC: 2 AN: 4764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67862

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000301 Hom.: 0

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.124G>A (p.V42I) alteration is located in exon 2 (coding exon 2) of the NT5DC1 gene. This alteration results from a G to A substitution at nucleotide position 124, causing the valine (V) at amino acid position 42 to be replaced by an isoleucine (I). 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	0.13
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.
PhyloP100		7.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.58	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.028	D;T
Sift4G	Benign	0.38	T;T
Polyphen		0.97	D;.
Vest4		0.39
MutPred		0.46		Gain of ubiquitination at K45 (P = 0.0913);Gain of ubiquitination at K45 (P = 0.0913);
MVP		0.25
MPC		0.42
ClinPred		0.25	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.61
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs562689401; hg19: chr6-116427437;