9-98056788-T-G

Variant names:

• chr9-98056788-T-G
• rs3199064
• NM_018946.4:c.-21T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018946.4(NANS):​c.-21T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,607,248 control chromosomes in the GnomAD database, including 189,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (28240 hom., cov: 33)
  • Exomes 𝑓: 0.46 (161214 hom.)
• Consequence: NANS NM_018946.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.899

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 9-98056788-T-G is Benign according to our data. Variant chr9-98056788-T-G is described in ClinVar as [Benign]. Clinvar id is 1238424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NANS	NM_018946.4	c.-21T>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000210444.6	NP_061819.2
TRIM14	XM_047424162.1	c.*29-20975A>C		intron_variant	Intron 6 of 6		XP_047280118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NANS	ENST00000210444	c.-21T>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_018946.4	ENSP00000210444.5
NANS	ENST00000480925.1	n.19T>G		non_coding_transcript_exon_variant	Exon 1 of 2	2
NANS	ENST00000495319.1	n.21T>G		non_coding_transcript_exon_variant	Exon 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86737 AN: 151982 Hom.: 28182 Cov.: 33

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.559

GnomAD2 exomes AF: 0.490 AC: 115025 AN: 234878 AF XY: 0.483

Gnomad AFR exome AF: 0.901

Gnomad AMR exome AF: 0.616

Gnomad ASJ exome AF: 0.401

Gnomad EAS exome AF: 0.318

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.462 AC: 672167 AN: 1455158 Hom.: 161214 Cov.: 57 AF XY: 0.463 AC XY: 335035 AN XY: 723918

Gnomad4 AFR exome AF: 0.911 AC: 30248 AN: 33212

Gnomad4 AMR exome AF: 0.610 AC: 26868 AN: 44030

Gnomad4 ASJ exome AF: 0.399 AC: 10367 AN: 25986

Gnomad4 EAS exome AF: 0.299 AC: 11782 AN: 39462

Gnomad4 SAS exome AF: 0.563 AC: 48258 AN: 85776

Gnomad4 FIN exome AF: 0.355 AC: 18130 AN: 51088

Gnomad4 NFE exome AF: 0.446 AC: 495422 AN: 1109978

Gnomad4 Remaining exome AF: 0.471 AC: 28268 AN: 59994

GnomAD4 genome AF: 0.571 AC: 86852 AN: 152090 Hom.: 28240 Cov.: 33 AF XY: 0.566 AC XY: 42058 AN XY: 74336

Gnomad4 AFR AF: 0.890 AC: 0.889873 AN: 0.889873

Gnomad4 AMR AF: 0.588 AC: 0.587793 AN: 0.587793

Gnomad4 ASJ AF: 0.412 AC: 0.411714 AN: 0.411714

Gnomad4 EAS AF: 0.322 AC: 0.322011 AN: 0.322011

Gnomad4 SAS AF: 0.574 AC: 0.574151 AN: 0.574151

Gnomad4 FIN AF: 0.356 AC: 0.356238 AN: 0.356238

Gnomad4 NFE AF: 0.437 AC: 0.436757 AN: 0.436757

Gnomad4 OTH AF: 0.559 AC: 0.559186 AN: 0.559186

Alfa AF: 0.487 Hom.: 25137

Bravo AF: 0.600

Asia WGS AF: 0.520 AC: 1795 AN: 3450

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.5
DANN	Benign	0.46
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=155/145	polymorphism

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: rs3199064; hg19: chr9-100819070; COSMIC: COSV52963324;