6-116117904-T-C

Variant names:

• chr6-116117904-T-C
• NM_152729.3:c.488T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152729.3(NT5DC1):​c.488T>C​(p.Val163Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NT5DC1 NM_152729.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.41
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31784496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3	c.488T>C	p.Val163Ala	missense_variant	Exon 6 of 12	ENST00000319550.9	NP_689942.2
NT5DC1	XM_006715378.4	c.488T>C	p.Val163Ala	missense_variant	Exon 6 of 10		XP_006715441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5DC1	ENST00000319550.9	c.488T>C	p.Val163Ala	missense_variant	Exon 6 of 12	1	NM_152729.3	ENSP00000326858.3
NT5DC1	ENST00000419791.3	c.488T>C	p.Val163Ala	missense_variant	Exon 6 of 7	3		ENSP00000393578.1
NT5DC1	ENST00000417846.2	n.229T>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
NT5DC1	ENST00000460749.1	n.-17T>C		upstream_gene_variant		5		ENSP00000433238.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.488T>C (p.V163A) alteration is located in exon 6 (coding exon 6) of the NT5DC1 gene. This alteration results from a T to C substitution at nucleotide position 488, causing the valine (V) at amino acid position 163 to be replaced by an alanine (A). 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	0.34
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T
Eigen	Benign	0.070
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.
PhyloP100		5.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.12
Sift	Benign	0.033	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.96	D;.
Vest4		0.36
MutPred		0.60		Loss of stability (P = 0.0762);Loss of stability (P = 0.0762);
MVP		0.33
MPC		0.15
ClinPred		0.91	D
GERP RS		4.6
Varity_R		0.12
gMVP		0.62
Mutation Taster		=77/23	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

hg19: chr6-116439067;