rs4237190

chr9-98081135-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018946.4(NANS):c.870+53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 1,602,124 control chromosomes in the GnomAD database, including 225,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (30828 hom., cov: 32)
  • Exomes 𝑓: 0.51 (195136 hom.)
• Consequence: NANS NM_018946.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.326

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.85618).
• BP6: Variant 9-98081135-A-G is Benign according to our data. Variant chr9-98081135-A-G is described in ClinVar as [Benign]. Clinvar id is 1278431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANS	NM_018946.4	c.870+53A>G		intron_variant		ENST00000210444.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANS	ENST00000210444.6	c.870+53A>G		intron_variant		1	NM_018946.4	P1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92349 AN: 152000 Hom.: 30779 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.593

GnomAD3 exomes AF: 0.544 AC: 133303 AN: 244834 Hom.: 38606 AF XY: 0.541 AC XY: 71581 AN XY: 132350

Gnomad AFR exome AF: 0.895

Gnomad AMR exome AF: 0.667

Gnomad ASJ exome AF: 0.445

Gnomad EAS exome AF: 0.363

Gnomad SAS exome AF: 0.670

Gnomad FIN exome AF: 0.384

Gnomad NFE exome AF: 0.491

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.511 AC: 740723 AN: 1450006 Hom.: 195136 Cov.: 35 AF XY: 0.513 AC XY: 369304 AN XY: 719212

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.662

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.608 AC: 92458 AN: 152118 Hom.: 30828 Cov.: 32 AF XY: 0.602 AC XY: 44777 AN XY: 74364

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.591

Alfa AF: 0.522 Hom.: 31673

Bravo AF: 0.635

TwinsUK AF: 0.504 AC: 1869

ALSPAC AF: 0.501 AC: 1931

ExAC AF: 0.548 AC: 66576

Asia WGS AF: 0.564 AC: 1965 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.99
Dann	Benign	0.42
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.019	N
MutationTaster	Benign	1.0	P;P
GERP RS		2.1

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

Other links and lift over

dbSNP: rs4237190; hg19: chr9-100843417; COSMIC: COSV52962982; COSMIC: COSV52962982;