Variant 9-98060802-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018946.4(NANS):c.153T>C(p.Ala51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,613,458 control chromosomes in the GnomAD database, including 231,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 30508 hom., cov: 33)

Exomes 𝑓: 0.52 ( 200518 hom. )

Consequence

NANS
NM_018946.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.117

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 9-98060802-T-C is Benign according to our data. Variant chr9-98060802-T-C is described in ClinVar as [Benign]. Clinvar id is 1250394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.117 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANS	NM_018946.4 linkuse as main transcript	c.153T>C	p.Ala51=	synonymous_variant	2/6	ENST00000210444.6
TRIM14	XM_047424162.1 linkuse as main transcript	c.*29-24989A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
NANS	ENST00000210444.6 linkuse as main transcript	c.153T>C	p.Ala51=	synonymous_variant	2/6	1	NM_018946.4	P1
NANS	ENST00000480925.1 linkuse as main transcript	n.192T>C		non_coding_transcript_exon_variant	2/2	2
NANS	ENST00000495319.1 linkuse as main transcript	n.194T>C		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.606

AC:

92099

AN:

152012

Hom.:

30453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

0.586

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.665

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.597

GnomAD3 exomes

AF:

0.542

AC:

136386

AN:

251458

Hom.:

39435

AF XY:

0.539

AC XY:

73289

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.881

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.444

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.668

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.496

Gnomad OTH exome

AF:

0.518

GnomAD4 exome

AF:

0.516

AC:

753969

AN:

1461328

Hom.:

200518

Cov.:

AF XY:

0.518

AC XY:

376842

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.889

Gnomad4 AMR exome

AF:

0.662

Gnomad4 ASJ exome

AF:

0.439

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.396

Gnomad4 NFE exome

AF:

0.503

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.606

AC:

92214

AN:

152130

Hom.:

30508

Cov.:

AF XY:

0.601

AC XY:

44653

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.870

Gnomad4 AMR

AF:

0.635

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.664

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.497

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.530

Hom.:

28881

Bravo

AF:

0.632

Asia WGS

AF:

0.553

AC:

1926

AN:

3478

EpiCase

AF:

0.491

EpiControl

AF:

0.505

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Spondyloepimetaphyseal dysplasia, Genevieve type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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