rs72728114

Variant names:

• chr1-99993238-G-A
• rs72728114
• NM_012243.3:c.-18-299G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-99993238-G-A
• chr1-99993238-G-C

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.-18-299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 221,402 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (64 hom., cov: 32)
  • Exomes 𝑓: 0.032 (43 hom.)
• Consequence: SLC35A3 NM_012243.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0260
• 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=-0.82).
• BP6: Variant 1-99993238-G-A is Benign according to our data. Variant chr1-99993238-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1189507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0248 (3781/152230) while in subpopulation NFE AF = 0.0397 (2702/68006). AF 95% confidence interval is 0.0385. There are 64 homozygotes in GnomAd4. There are 1784 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 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.-18-299G>A		intron	N/A	NP_036375.1	Q9Y2D2-1
	SLC35A3	NM_001271685.2		c.109-299G>A		intron	N/A	NP_001258614.1	Q9Y2D2-2
	SLC35A3	NM_001438725.1		c.-18-299G>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.-18-299G>A		intron	N/A	ENSP00000433849.1	Q9Y2D2-1
	ENSG00000283761	ENST00000639037.1	TSL:5	c.-18-299G>A		intron	N/A	ENSP00000492745.1	A0A1W2PSA9
	SLC35A3	ENST00000638336.1	TSL:1	c.-18-299G>A		intron	N/A	ENSP00000491145.1	Q9Y2D2-3

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3785 AN: 152112 Hom.: 64 Cov.: 32

Gnomad AFR AF: 0.00705

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00747

Gnomad FIN AF: 0.0296

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0318 AC: 2198 AN: 69172 Hom.: 43 AF XY: 0.0312 AC XY: 1144 AN XY: 36720

African (AFR) AF: 0.00614 AC: 8 AN: 1302

American (AMR) AF: 0.0213 AC: 69 AN: 3232

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 70 AN: 1798

East Asian (EAS) AF: 0.000288 AC: 1 AN: 3474

South Asian (SAS) AF: 0.00957 AC: 77 AN: 8046

European-Finnish (FIN) AF: 0.0363 AC: 111 AN: 3062

Middle Eastern (MID) AF: 0.0273 AC: 7 AN: 256

European-Non Finnish (NFE) AF: 0.0392 AC: 1727 AN: 44030

Other (OTH) AF: 0.0322 AC: 128 AN: 3972

GnomAD4 genome AF: 0.0248 AC: 3781 AN: 152230 Hom.: 64 Cov.: 32 AF XY: 0.0240 AC XY: 1784 AN XY: 74444

African (AFR) AF: 0.00700 AC: 291 AN: 41542

American (AMR) AF: 0.0148 AC: 227 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00747 AC: 36 AN: 4818

European-Finnish (FIN) AF: 0.0296 AC: 314 AN: 10598

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2702 AN: 68006

Other (OTH) AF: 0.0241 AC: 51 AN: 2114

Alfa AF: 0.0331 Hom.: 162

Bravo AF: 0.0238

Asia WGS AF: 0.00375 AC: 14 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	-0.82
CADD	Benign	4.1
DANN	Benign	0.51
PhyloP100		-0.026
Mutation Taster		=100/0	polymorphism

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: rs72728114; hg19: chr1-100458794;