1-99970713-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124904230 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A3	NM_012243.3	c.-19+551T>A		intron_variant		ENST00000533028.8
LOC124904230	XR_007066249.1	n.280-30643A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A3	ENST00000533028.8	c.-19+551T>A		intron_variant		1	NM_012243.3	P1

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

Gnomad4 AFR exome AF: 0.00291

Gnomad4 AMR exome AF: 0.00667

Gnomad4 ASJ exome AF: 0.00761

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000471

Gnomad4 FIN exome AF: 0.00631

Gnomad4 NFE exome AF: 0.0164

Gnomad4 OTH exome AF: 0.0114

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

Gnomad4 AFR AF: 0.00317

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00489

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.0128 Hom.: 2

Bravo AF: 0.00998

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 20, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	3.7
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs114502977; hg19: chr1-100436269;