Variant chr9-98056788-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018946.4(NANS):c.-21T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,607,248 control chromosomes in the GnomAD database, including 189,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 28240 hom., cov: 33)

Exomes 𝑓: 0.46 ( 161214 hom. )

Consequence

NANS
NM_018946.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.899

Variant links:

Genes affected

NANS (HGNC:19237): (N-acetylneuraminate synthase) This gene encodes an enzyme that functions in the biosynthetic pathways of sialic acids. In vitro, the encoded protein uses N-acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates to generate phosphorylated forms of N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), respectively; however, it exhibits much higher activity toward the Neu5Ac phosphate product. In insect cells, expression of this gene results in Neu5Ac and KDN production. This gene is related to the E. coli sialic acid synthase gene neuB, and it can partially restore sialic acid synthase activity in an E. coli neuB-negative mutant. [provided by RefSeq, Jul 2008]

NANS links:

TRIM14 (HGNC:):

TRIM14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 9-98056788-T-G is Benign according to our data. Variant chr9-98056788-T-G is described in ClinVar as [Benign]. Clinvar id is 1238424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NANS	NM_018946.4 linkuse as main transcript	c.-21T>G		5_prime_UTR_variant	1/6	ENST00000210444.6	NP_061819.2
TRIM14	XM_047424162.1 linkuse as main transcript	c.*29-20975A>C		intron_variant			XP_047280118.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
NANS	ENST00000210444.6 linkuse as main transcript	c.-21T>G	5_prime_UTR_variant	1/6	1	NM_018946.4	ENSP00000210444	P1
NANS	ENST00000480925.1 linkuse as main transcript	n.19T>G	non_coding_transcript_exon_variant	1/2	2
NANS	ENST00000495319.1 linkuse as main transcript	n.21T>G	non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86737

AN:

151982

Hom.:

28182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.587

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.575

Gnomad FIN

AF:

0.356

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.437

Gnomad OTH

AF:

0.559

GnomAD3 exomes

AF:

0.490

AC:

115025

AN:

234878

Hom.:

30504

AF XY:

0.483

AC XY:

62243

AN XY:

128946

show subpopulations

Gnomad AFR exome

AF:

0.901

Gnomad AMR exome

AF:

0.616

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.572

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.434

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.462

AC:

672167

AN:

1455158

Hom.:

161214

Cov.:

AF XY:

0.463

AC XY:

335035

AN XY:

723918

show subpopulations

Gnomad4 AFR exome

AF:

0.911

Gnomad4 AMR exome

AF:

0.610

Gnomad4 ASJ exome

AF:

0.399

Gnomad4 EAS exome

AF:

0.299

Gnomad4 SAS exome

AF:

0.563

Gnomad4 FIN exome

AF:

0.355

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.471

GnomAD4 genome

AF:

0.571

AC:

86852

AN:

152090

Hom.:

28240

Cov.:

AF XY:

0.566

AC XY:

42058

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.890

Gnomad4 AMR

AF:

0.588

Gnomad4 ASJ

AF:

0.412

Gnomad4 EAS

AF:

0.322

Gnomad4 SAS

AF:

0.574

Gnomad4 FIN

AF:

0.356

Gnomad4 NFE

AF:

0.437

Gnomad4 OTH

AF:

0.559

Alfa

AF:

0.470

Hom.:

18230

Bravo

AF:

0.600

Asia WGS

AF:

0.520

AC:

1795

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

4.5

DANN

Benign

0.46

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over