NM_018946.4:c.132+17dupC

Variant names:

• chr9-98056954-T-TC
• rs760068312
• NM_018946.4:c.132+17dupC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_018946.4(NANS):​c.132+17dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 1,566,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NANS NM_018946.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.222
• Publications: 0 publications found

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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 9-98056954-T-TC is Benign according to our data. Variant chr9-98056954-T-TC is described in ClinVar as Likely_benign. ClinVar VariationId is 2719918.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018946.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANS	NM_018946.4	MANE Select	c.132+17dupC		intron	N/A	NP_061819.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NANS	ENST00000210444.6	TSL:1 MANE Select	c.132+17dupC		intron	N/A	ENSP00000210444.5	Q9NR45
	NANS	ENST00000924305.1		c.132+17dupC		intron	N/A	ENSP00000594364.1
	NANS	ENST00000924304.1		c.132+17dupC		intron	N/A	ENSP00000594363.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151962 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000524 AC: 1 AN: 190736 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000715

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1414058 Hom.: 0 Cov.: 34 AF XY: 0.00000143 AC XY: 1 AN XY: 699752

African (AFR) AF: 0.00 AC: 0 AN: 29644

American (AMR) AF: 0.00 AC: 0 AN: 40596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24052

East Asian (EAS) AF: 0.0000554 AC: 2 AN: 36132

South Asian (SAS) AF: 0.00 AC: 0 AN: 81632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4966

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088532

Other (OTH) AF: 0.00 AC: 0 AN: 58084

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151962 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74218

African (AFR) AF: 0.00 AC: 0 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.22

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

Other links and lift over

dbSNP: rs760068312; hg19: chr9-100819236;