9-98060802-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_018946.4(NANS):c.153T>C(p.Ala51Ala) 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:4

Conservation

PhyloP100: 0.117

Publications

22 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein
NANS	NM_018946.4 link	c.153T>C	p.Ala51Ala	synonymous_variant	Exon 2 of 6	ENST00000210444.6	NP_061819.2
TRIM14	XM_047424162.1 link	c.*29-24989A>G		intron_variant	Intron 6 of 6		XP_047280118.1
NANS	XM_011518787.3 link	c.-359T>C		upstream_gene_variant			XP_011517089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NANS	ENST00000210444.6 link	c.153T>C	p.Ala51Ala	synonymous_variant	Exon 2 of 6	1	NM_018946.4	ENSP00000210444.5	Q9NR45
NANS	ENST00000480925.1 link	n.192T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2
NANS	ENST00000495319.1 link	n.194T>C		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes

AF:

0.542

AC:

136386

AN:

251458

AF XY:

0.539

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 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

African (AFR)

AF:

0.889

AC:

29777

AN:

33478

American (AMR)

AF:

0.662

AC:

29612

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

11483

AN:

26128

East Asian (EAS)

AF:

0.301

AC:

11958

AN:

39690

South Asian (SAS)

AF:

0.656

AC:

56554

AN:

86244

European-Finnish (FIN)

AF:

0.396

AC:

21140

AN:

53410

Middle Eastern (MID)

AF:

0.548

AC:

3158

AN:

5768

European-Non Finnish (NFE)

AF:

0.503

AC:

558978

AN:

1111510

Other (OTH)

AF:

0.519

AC:

31309

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

19652

39304

58957

78609

98261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.606

AC:

92214

AN:

152130

Hom.:

30508

Cov.:

AF XY:

0.601

AC XY:

44653

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.870

AC:

36137

AN:

41530

American (AMR)

AF:

0.635

AC:

9707

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1544

AN:

3470

East Asian (EAS)

AF:

0.324

AC:

1676

AN:

5178

South Asian (SAS)

AF:

0.664

AC:

3199

AN:

4816

European-Finnish (FIN)

AF:

0.398

AC:

4201

AN:

10566

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.497

AC:

33802

AN:

67970

Other (OTH)

AF:

0.595

AC:

1255

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1659

3318

4976

6635

8294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.543

Hom.:

37545

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:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Spondyloepimetaphyseal dysplasia, Genevieve type

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=81/19

polymorphism (auto)

(source)

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

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9-98060802-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over