NM_012243.3:c.-19+551T>A

Variant names:

• chr1-99970713-T-A
• rs114502977
• NM_012243.3:c.-19+551T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_012243.3(SLC35A3):​c.-19+551T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,032,910 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (16 hom., cov: 32)
  • Exomes 𝑓: 0.013 (110 hom.)
• Consequence: SLC35A3 NM_012243.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.104
• 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, PanelApp Australia

ENSG00000283761 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 1-99970713-T-A is Benign according to our data. Variant chr1-99970713-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1218622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00984 (1499/152356) while in subpopulation NFE AF = 0.0165 (1120/68028). AF 95% confidence interval is 0.0157. There are 16 homozygotes in GnomAd4. There are 663 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012243.3. 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
	SLC35A3	NM_012243.3	MANE Select	c.-19+551T>A		intron	N/A	NP_036375.1	Q9Y2D2-1
	SLC35A3	NM_001271685.2		c.108+69T>A		intron	N/A	NP_001258614.1	Q9Y2D2-2
	SLC35A3	NM_001438725.1		c.-118+551T>A		intron	N/A	NP_001425654.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A3	ENST00000533028.8	TSL:1 MANE Select	c.-19+551T>A		intron	N/A	ENSP00000433849.1	Q9Y2D2-1
	ENSG00000283761	ENST00000639037.1	TSL:5	c.-19+551T>A		intron	N/A	ENSP00000492745.1	A0A1W2PSA9
	SLC35A3	ENST00000638336.1	TSL:1	c.-19+551T>A		intron	N/A	ENSP00000491145.1	Q9Y2D2-3

Frequencies

GnomAD3 genomes AF: 0.00985 AC: 1500 AN: 152238 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00318

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00765

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.0130 AC: 11477 AN: 880554 Hom.: 110 AF XY: 0.0127 AC XY: 5732 AN XY: 452448

African (AFR) AF: 0.00291 AC: 61 AN: 20990

American (AMR) AF: 0.00667 AC: 196 AN: 29364

Ashkenazi Jewish (ASJ) AF: 0.00761 AC: 155 AN: 20358

East Asian (EAS) AF: 0.00 AC: 0 AN: 32830

South Asian (SAS) AF: 0.000471 AC: 31 AN: 65886

European-Finnish (FIN) AF: 0.00631 AC: 208 AN: 32972

Middle Eastern (MID) AF: 0.00108 AC: 5 AN: 4620

European-Non Finnish (NFE) AF: 0.0164 AC: 10355 AN: 632682

Other (OTH) AF: 0.0114 AC: 466 AN: 40852

GnomAD4 genome AF: 0.00984 AC: 1499 AN: 152356 Hom.: 16 Cov.: 32 AF XY: 0.00890 AC XY: 663 AN XY: 74506

African (AFR) AF: 0.00317 AC: 132 AN: 41578

American (AMR) AF: 0.00758 AC: 116 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00489 AC: 52 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0165 AC: 1120 AN: 68028

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.0128 Hom.: 2

Bravo AF: 0.00998

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.7
DANN	Benign	0.78
PhyloP100		0.10
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114502977; hg19: chr1-100436269;