Variant 9-98056910-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_018946.4(NANS):c.102C>T(p.Asp34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,608,508 control chromosomes in the GnomAD database, including 56,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 10900 hom., cov: 33)

Exomes 𝑓: 0.23 ( 45216 hom. )

Consequence

NANS
NM_018946.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.05

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 9-98056910-C-T is Benign according to our data. Variant chr9-98056910-C-T is described in ClinVar as [Benign]. Clinvar id is 1241755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 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.102C>T	p.Asp34=	synonymous_variant	1/6	ENST00000210444.6	NP_061819.2
TRIM14	XM_047424162.1 linkuse as main transcript	c.*29-21097G>A		intron_variant			XP_047280118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NANS	ENST00000210444.6 linkuse as main transcript	c.102C>T	p.Asp34=	synonymous_variant	1/6	1	NM_018946.4	ENSP00000210444	P1
NANS	ENST00000480925.1 linkuse as main transcript	n.141C>T		non_coding_transcript_exon_variant	1/2	2
NANS	ENST00000495319.1 linkuse as main transcript	n.143C>T		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49610

AN:

152024

Hom.:

10886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.618

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.250

Gnomad ASJ

AF:

0.231

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.303

GnomAD3 exomes

AF:

0.265

AC:

63603

AN:

239692

Hom.:

10900

AF XY:

0.272

AC XY:

35529

AN XY:

130804

show subpopulations

Gnomad AFR exome

AF:

0.631

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.117

Gnomad SAS exome

AF:

0.499

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.229

AC:

333033

AN:

1456368

Hom.:

45216

Cov.:

AF XY:

0.235

AC XY:

170573

AN XY:

724506

show subpopulations

Gnomad4 AFR exome

AF:

0.641

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.226

Gnomad4 EAS exome

AF:

0.0954

Gnomad4 SAS exome

AF:

0.488

Gnomad4 FIN exome

AF:

0.205

Gnomad4 NFE exome

AF:

0.200

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.326

AC:

49666

AN:

152140

Hom.:

10900

Cov.:

AF XY:

0.327

AC XY:

24311

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.618

Gnomad4 AMR

AF:

0.250

Gnomad4 ASJ

AF:

0.231

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.494

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.244

Hom.:

3981

Bravo

AF:

0.336

Asia WGS

AF:

0.345

AC:

1203

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

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

-0.31

CADD

Benign

8.0

DANN

Benign

0.95

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

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