rs13118

Variant names:

• chr6-31859509-A-T
• rs13118
• NM_000434.4:c.*210T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31859509-A-T
• chr6-31859509-A-G

Variant summary

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

The NM_000434.4(NEU1):​c.*210T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 657,548 control chromosomes in the GnomAD database, including 813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (279 hom., cov: 32)
  • Exomes 𝑓: 0.039 (534 hom.)
• Consequence: NEU1 NM_000434.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.112
• Publications: 22 publications found

Genes affected

NEU1 (HGNC:7758): (neuraminidase 1) The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity. [provided by RefSeq, Jul 2008]

NEU1 Gene-Disease associations (from GenCC):

• sialidosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• sialidosis type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• congenital sialidosis type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• juvenile sialidosis type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• sialidosis type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-31859509-A-T is Benign according to our data. Variant chr6-31859509-A-T is described in ClinVar as Benign. ClinVar VariationId is 356229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000434.4. 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
	NEU1	NM_000434.4	MANE Select	c.*210T>A		3_prime_UTR	Exon 6 of 6	NP_000425.1	Q5JQI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEU1	ENST00000375631.5	TSL:1 MANE Select	c.*210T>A		3_prime_UTR	Exon 6 of 6	ENSP00000364782.4	Q99519
	NEU1	ENST00000850553.1		c.*210T>A		3_prime_UTR	Exon 6 of 6	ENSP00000520846.1	A0ABB0MVI7
	NEU1	ENST00000877813.1		c.*210T>A		3_prime_UTR	Exon 6 of 6	ENSP00000547872.1

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7935 AN: 152170 Hom.: 278 Cov.: 32

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.0273

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0329

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0385 AC: 19456 AN: 505260 Hom.: 534 Cov.: 4 AF XY: 0.0379 AC XY: 10239 AN XY: 270388

African (AFR) AF: 0.101 AC: 1468 AN: 14502

American (AMR) AF: 0.0305 AC: 911 AN: 29880

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 1363 AN: 16518

East Asian (EAS) AF: 0.0588 AC: 1863 AN: 31690

South Asian (SAS) AF: 0.0277 AC: 1499 AN: 54138

European-Finnish (FIN) AF: 0.0322 AC: 1007 AN: 31284

Middle Eastern (MID) AF: 0.0580 AC: 130 AN: 2242

European-Non Finnish (NFE) AF: 0.0339 AC: 10068 AN: 296590

Other (OTH) AF: 0.0404 AC: 1147 AN: 28416

GnomAD4 genome AF: 0.0522 AC: 7944 AN: 152288 Hom.: 279 Cov.: 32 AF XY: 0.0523 AC XY: 3892 AN XY: 74468

African (AFR) AF: 0.100 AC: 4154 AN: 41552

American (AMR) AF: 0.0303 AC: 463 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 257 AN: 3472

East Asian (EAS) AF: 0.0376 AC: 195 AN: 5182

South Asian (SAS) AF: 0.0271 AC: 131 AN: 4830

European-Finnish (FIN) AF: 0.0344 AC: 365 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0329 AC: 2239 AN: 68020

Other (OTH) AF: 0.0534 AC: 113 AN: 2116

Alfa AF: 0.0412 Hom.: 91

Bravo AF: 0.0555

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Sialidosis type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.62
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs13118; hg19: chr6-31827286;