Variant rs4237190 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 ENST00000210444.6(NANS):c.870+53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,602,124 control chromosomes in the GnomAD database, including 225,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 30828 hom., cov: 32)

Exomes 𝑓: 0.51 ( 195136 hom. )

Consequence

NANS
ENST00000210444.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.326

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:16283): (tripartite motif containing 14) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies and its function has not been determined. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

TRIM14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.85618).

BP6

Variant 9-98081135-A-G is Benign according to our data. Variant chr9-98081135-A-G is described in ClinVar as [Benign]. Clinvar id is 1278431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 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.870+53A>G		intron_variant		ENST00000210444.6	NP_061819.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NANS	ENST00000210444.6 linkuse as main transcript	c.870+53A>G		intron_variant		1	NM_018946.4	ENSP00000210444	P1

Frequencies

GnomAD3 genomes

AF:

0.608

AC:

92349

AN:

152000

Hom.:

30779

Cov.:

show subpopulations

Gnomad AFR

AF:

0.885

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.634

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.668

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.593

GnomAD3 exomes

AF:

0.544

AC:

133303

AN:

244834

Hom.:

38606

AF XY:

0.541

AC XY:

71581

AN XY:

132350

show subpopulations

Gnomad AFR exome

AF:

0.895

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.670

Gnomad FIN exome

AF:

0.384

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.514

GnomAD4 exome

AF:

0.511

AC:

740723

AN:

1450006

Hom.:

195136

Cov.:

AF XY:

0.513

AC XY:

369304

AN XY:

719212

show subpopulations

Gnomad4 AFR exome

AF:

0.904

Gnomad4 AMR exome

AF:

0.662

Gnomad4 ASJ exome

AF:

0.438

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.658

Gnomad4 FIN exome

AF:

0.385

Gnomad4 NFE exome

AF:

0.495

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.608

AC:

92458

AN:

152118

Hom.:

30828

Cov.:

AF XY:

0.602

AC XY:

44777

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.885

Gnomad4 AMR

AF:

0.634

Gnomad4 ASJ

AF:

0.444

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.667

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.591

Alfa

AF:

0.522

Hom.:

31673

Bravo

AF:

0.635

TwinsUK

AF:

0.504

AC:

1869

ALSPAC

AF:

0.501

AC:

1931

ExAC

AF:

0.548

AC:

66576

Asia WGS

AF:

0.564

AC:

1965

AN:

3478

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_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.99

DANN

Benign

0.42

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

MutationTaster

Benign

1.0

P;P

GERP RS

2.1

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