9-98060658-G-A

Position:

• chr9-98060658-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018946.4(NANS):​c.133-124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 979,086 control chromosomes in the GnomAD database, including 36,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (10691 hom., cov: 32)
  • Exomes 𝑓: 0.23 (25796 hom.)
• Consequence: NANS NM_018946.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 9-98060658-G-A is Benign according to our data. Variant chr9-98060658-G-A is described in ClinVar as [Benign]. Clinvar id is 1247387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NANS	NM_018946.4	c.133-124G>A		intron_variant		ENST00000210444.6	NP_061819.2
TRIM14	XM_047424162.1	c.*29-24845C>T		intron_variant			XP_047280118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NANS	ENST00000210444.6	c.133-124G>A		intron_variant		1	NM_018946.4	ENSP00000210444	P1
NANS	ENST00000480925.1	n.172-124G>A		intron_variant, non_coding_transcript_variant		2
NANS	ENST00000495319.1	n.174-124G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49101 AN: 151824 Hom.: 10681 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.226 AC: 186961 AN: 827144 Hom.: 25796 AF XY: 0.235 AC XY: 99863 AN XY: 424960

Gnomad4 AFR exome AF: 0.628

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.0928

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.323 AC: 49153 AN: 151942 Hom.: 10691 Cov.: 32 AF XY: 0.324 AC XY: 24049 AN XY: 74248

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.302

Alfa AF: 0.259 Hom.: 874

Bravo AF: 0.333

Asia WGS AF: 0.348 AC: 1216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.40

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: rs7846880; hg19: chr9-100822940;