chr9-98056910-C-T

Variant names:

• chr9-98056910-C-T
• rs3739670
• NM_018946.4:c.102C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_018946.4(NANS):​c.102C>T​(p.Asp34Asp) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.05
• Publications: 14 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018946.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANS	NM_018946.4	MANE Select	c.102C>T	p.Asp34Asp	synonymous	Exon 1 of 6	NP_061819.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANS	ENST00000210444.6	TSL:1 MANE Select	c.102C>T	p.Asp34Asp	synonymous	Exon 1 of 6	ENSP00000210444.5	Q9NR45
	NANS	ENST00000924305.1		c.102C>T	p.Asp34Asp	synonymous	Exon 1 of 7	ENSP00000594364.1
	NANS	ENST00000924304.1		c.102C>T	p.Asp34Asp	synonymous	Exon 1 of 6	ENSP00000594363.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49610 AN: 152024 Hom.: 10886 Cov.: 33

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

GnomAD2 exomes AF: 0.265 AC: 63603 AN: 239692 AF XY: 0.272

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 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.: 39 AF XY: 0.235 AC XY: 170573 AN XY: 724506

African (AFR) AF: 0.641 AC: 20952 AN: 32698

American (AMR) AF: 0.234 AC: 10391 AN: 44398

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5862 AN: 25900

East Asian (EAS) AF: 0.0954 AC: 3746 AN: 39252

South Asian (SAS) AF: 0.488 AC: 41868 AN: 85876

European-Finnish (FIN) AF: 0.205 AC: 10778 AN: 52584

Middle Eastern (MID) AF: 0.376 AC: 2133 AN: 5678

European-Non Finnish (NFE) AF: 0.200 AC: 222271 AN: 1109846

Other (OTH) AF: 0.250 AC: 15032 AN: 60136

GnomAD4 genome AF: 0.326 AC: 49666 AN: 152140 Hom.: 10900 Cov.: 33 AF XY: 0.327 AC XY: 24311 AN XY: 74386

African (AFR) AF: 0.618 AC: 25655 AN: 41510

American (AMR) AF: 0.250 AC: 3823 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 799 AN: 3464

East Asian (EAS) AF: 0.126 AC: 649 AN: 5164

South Asian (SAS) AF: 0.494 AC: 2384 AN: 4830

European-Finnish (FIN) AF: 0.213 AC: 2261 AN: 10602

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13251 AN: 67962

Other (OTH) AF: 0.304 AC: 642 AN: 2110

Alfa AF: 0.247 Hom.: 4478

Bravo AF: 0.336

Asia WGS AF: 0.345 AC: 1203 AN: 3474

ClinVar

ClinVar submissions

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	-0.31
CADD	Benign	8.0
DANN	Benign	0.95
PhyloP100		-2.1
PromoterAI		-0.037	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=96/4	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: rs3739670; hg19: chr9-100819192; COSMIC: COSV52963098;