6-116106308-A-G

Variant names:

• chr6-116106308-A-G
• rs140387594
• NM_152729.3:c.158A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_152729.3(NT5DC1):​c.158A>G​(p.Asn53Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,573,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: NT5DC1 NM_152729.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.147
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018475384).
• BP6: Variant 6-116106308-A-G is Benign according to our data. Variant chr6-116106308-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2461031.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3	c.158A>G	p.Asn53Ser	missense_variant	Exon 2 of 12	ENST00000319550.9	NP_689942.2
NT5DC1	XM_006715378.4	c.158A>G	p.Asn53Ser	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.158A>G	p.Asn53Ser	missense_variant	Exon 2 of 12	1	NM_152729.3	ENSP00000326858.3
NT5DC1	ENST00000419791.3	c.158A>G	p.Asn53Ser	missense_variant	Exon 2 of 7	3		ENSP00000393578.1

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 150260 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 251006 AF XY: 0.0000295

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000232 AC: 33 AN: 1423580 Hom.: 0 Cov.: 26 AF XY: 0.0000239 AC XY: 17 AN XY: 710620

African (AFR) AF: 0.00 AC: 0 AN: 32710

American (AMR) AF: 0.000112 AC: 5 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.0000586 AC: 5 AN: 85378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.000537 AC: 3 AN: 5582

European-Non Finnish (NFE) AF: 0.0000158 AC: 17 AN: 1077538

Other (OTH) AF: 0.0000509 AC: 3 AN: 58992

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 150316 Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1 AN XY: 73234

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

African (AFR) AF: 0.00 AC: 0 AN: 41012

American (AMR) AF: 0.00 AC: 0 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5132

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67792

Other (OTH) AF: 0.00 AC: 0 AN: 2076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.004005), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 06, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.54
DEOGEN2	Benign	0.0062	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.018	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.86	L;.
PhyloP100		-0.15
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.10	N;N
REVEL	Benign	0.021
Sift	Benign	0.89	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.0030	B;.
Vest4		0.097
MVP		0.067
MPC		0.097
ClinPred		0.022	T
GERP RS		-0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.29
Mutation Taster		=95/5	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: rs140387594; hg19: chr6-116427471;