9-98060558-T-A

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.133-224T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 151,938 control chromosomes in the GnomAD database, including 8,400 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (8400 hom., cov: 32)
• Consequence: NANS NM_018946.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.533

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-98060558-T-A is Benign according to our data. Variant chr9-98060558-T-A is described in ClinVar as [Benign]. Clinvar id is 1250825.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NANS	NM_018946.4	c.133-224T>A		intron_variant		ENST00000210444.6
TRIM14	XM_047424162.1	c.*29-24745A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NANS	ENST00000210444.6	c.133-224T>A		intron_variant		1	NM_018946.4	P1
NANS	ENST00000480925.1	n.172-224T>A		intron_variant, non_coding_transcript_variant		2
NANS	ENST00000495319.1	n.174-224T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45080 AN: 151822 Hom.: 8395 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.280

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.297 AC: 45113 AN: 151938 Hom.: 8400 Cov.: 32 AF XY: 0.298 AC XY: 22158 AN XY: 74258

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.281

Alfa AF: 0.241 Hom.: 685

Bravo AF: 0.302

Asia WGS AF: 0.342 AC: 1193 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	-0.87
Cadd	Benign	12
Dann	Benign	0.90

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: rs7038592; hg19: chr9-100822840;