rs1553204463

Variant names:

• chr1-100017821-AT-A
• rs1553204463
• NM_012243.3:c.887+7delT

Variant summary

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

The NM_012243.3(SLC35A3):​c.887+7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000433 in 1,387,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: SLC35A3 NM_012243.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.648
• Publications: 0 publications found

Genes affected

SLC35A3 (HGNC:11023): (solute carrier family 35 member A3) This gene encodes a UDP-N-acetylglucosamine transporter found in the golgi apparatus membrane. In cattle, a missense mutation in this gene causes complex vertebral malformation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SLC35A3 Gene-Disease associations (from GenCC):

• autism spectrum disorder - epilepsy - arthrogryposis syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000283761 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-100017821-AT-A is Benign according to our data. Variant chr1-100017821-AT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 541620.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A3	NM_012243.3	c.887+7delT		splice_region_variant, intron_variant	Intron 7 of 7	ENST00000533028.8	NP_036375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A3	ENST00000533028.8	c.887+7delT		splice_region_variant, intron_variant	Intron 7 of 7	1	NM_012243.3	ENSP00000433849.1
ENSG00000283761	ENST00000639037.1	c.753+2402delT		intron_variant	Intron 6 of 16	5		ENSP00000492745.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000433 AC: 6 AN: 1387234 Hom.: 0 Cov.: 25 AF XY: 0.00000434 AC XY: 3 AN XY: 690810

African (AFR) AF: 0.00 AC: 0 AN: 29308

American (AMR) AF: 0.00 AC: 0 AN: 30890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24686

East Asian (EAS) AF: 0.00 AC: 0 AN: 36796

South Asian (SAS) AF: 0.00 AC: 0 AN: 74766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4656

European-Non Finnish (NFE) AF: 0.00000558 AC: 6 AN: 1076004

Other (OTH) AF: 0.00 AC: 0 AN: 57250

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autism spectrum disorder - epilepsy - arthrogryposis syndrome Benign:1

Nov 22, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.65

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: rs1553204463; hg19: chr1-100483377;