9-98060802-T-C

Variant names:

• chr9-98060802-T-C
• rs13049
• NM_018946.4:c.153T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000210444.6(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 ENST00000210444.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.117
• Publications: 22 publications found

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]

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]

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000210444.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANS	NM_018946.4	MANE Select	c.153T>C	p.Ala51Ala	synonymous	Exon 2 of 6	NP_061819.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANS	ENST00000210444.6	TSL:1 MANE Select	c.153T>C	p.Ala51Ala	synonymous	Exon 2 of 6	ENSP00000210444.5
	NANS	ENST00000480925.1	TSL:2	n.192T>C		non_coding_transcript_exon	Exon 2 of 2
	NANS	ENST00000495319.1	TSL:3	n.194T>C		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92099 AN: 152012 Hom.: 30453 Cov.: 33

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

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.: 52 AF XY: 0.518 AC XY: 376842 AN XY: 727030

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

GnomAD4 genome AF: 0.606 AC: 92214 AN: 152130 Hom.: 30508 Cov.: 33 AF XY: 0.601 AC XY: 44653 AN XY: 74354

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

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Spondyloepimetaphyseal dysplasia, Genevieve type (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
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)

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

Other links and lift over

dbSNP: rs13049; hg19: chr9-100823084; COSMIC: COSV52965592;