rs2281732

Variant names:

• chr9-98082725-A-G
• rs2281732
• NM_018946.4:c.871-121A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Benign. The variant received -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 VariationId 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.

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.871-121A>G		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.871-121A>G		intron	N/A	ENSP00000210444.5	Q9NR45
	TRIM14	ENST00000869646.1		c.*871T>C		3_prime_UTR	Exon 7 of 7	ENSP00000539705.1
	TRIM14	ENST00000869648.1		c.*524T>C		3_prime_UTR	Exon 7 of 7	ENSP00000539707.1

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

African (AFR) AF: 0.574 AC: 9886 AN: 17228

American (AMR) AF: 0.227 AC: 5995 AN: 26430

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 3636 AN: 16350

East Asian (EAS) AF: 0.0927 AC: 2996 AN: 32316

South Asian (SAS) AF: 0.494 AC: 26693 AN: 54060

European-Finnish (FIN) AF: 0.191 AC: 7281 AN: 38102

Middle Eastern (MID) AF: 0.354 AC: 881 AN: 2490

European-Non Finnish (NFE) AF: 0.194 AC: 88887 AN: 458848

Other (OTH) AF: 0.249 AC: 8369 AN: 33670

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

African (AFR) AF: 0.563 AC: 23345 AN: 41444

American (AMR) AF: 0.236 AC: 3617 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 805 AN: 3470

East Asian (EAS) AF: 0.127 AC: 658 AN: 5180

South Asian (SAS) AF: 0.500 AC: 2408 AN: 4818

European-Finnish (FIN) AF: 0.201 AC: 2129 AN: 10596

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13015 AN: 68004

Other (OTH) AF: 0.286 AC: 605 AN: 2114

Alfa AF: 0.246 Hom.: 2047

Bravo AF: 0.316

Asia WGS AF: 0.344 AC: 1199 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2281732;

hg19: chr9-100845007;