rs2281732

Positions:

• chr9-98082725-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.871-121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 831,620 control chromosomes in the GnomAD database, including 30,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (9346 hom., cov: 32)
  • Exomes 𝑓: 0.23 (21502 hom.)
• Consequence: NANS NM_018946.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.125

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_noAF=-0.84).
• BP6: Variant 9-98082725-A-G is Benign according to our data. Variant chr9-98082725-A-G is described in ClinVar as [Benign]. Clinvar id is 1272811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANS	NM_018946.4	c.871-121A>G		intron_variant		ENST00000210444.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANS	ENST00000210444.6	c.871-121A>G		intron_variant		1	NM_018946.4	P1
TRIM14	ENST00000375098.7	c.*28+4717T>C		intron_variant		2		P1
NANS	ENST00000461452.1	n.2798-121A>G		intron_variant, non_coding_transcript_variant		2
TRIM14	ENST00000478530.1	n.561-1464T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46746 AN: 152008 Hom.: 9336 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.228 AC: 154624 AN: 679494 Hom.: 21502 AF XY: 0.237 AC XY: 83026 AN XY: 349724

Gnomad4 AFR exome AF: 0.574

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.0927

Gnomad4 SAS exome AF: 0.494

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.308 AC: 46788 AN: 152126 Hom.: 9346 Cov.: 32 AF XY: 0.308 AC XY: 22895 AN XY: 74356

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.286

Alfa AF: 0.236 Hom.: 1456

Bravo AF: 0.316

Asia WGS AF: 0.344 AC: 1199 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_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2281732; hg19: chr9-100845007;