1-99997304-T-C

Variant names:

• chr1-99997304-T-C
• rs7530361
• NM_012243.3:c.188-1957T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012243.3(SLC35A3):​c.188-1957T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 150,002 control chromosomes in the GnomAD database, including 7,187 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (7187 hom., cov: 28)
• Consequence: SLC35A3 NM_012243.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A3	NM_012243.3	MANE Select	c.188-1957T>C		intron	N/A	NP_036375.1
	SLC35A3	NM_001271685.2		c.314-1957T>C		intron	N/A	NP_001258614.1
	SLC35A3	NM_001438725.1		c.188-1957T>C		intron	N/A	NP_001425654.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A3	ENST00000533028.8	TSL:1 MANE Select	c.188-1957T>C		intron	N/A	ENSP00000433849.1
	ENSG00000283761	ENST00000639037.1	TSL:5	c.188-1957T>C		intron	N/A	ENSP00000492745.1
	SLC35A3	ENST00000638336.1	TSL:1	c.188-1957T>C		intron	N/A	ENSP00000491145.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37272 AN: 149898 Hom.: 7159 Cov.: 28

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0552

Gnomad SAS AF: 0.0980

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.249 AC: 37342 AN: 150002 Hom.: 7187 Cov.: 28 AF XY: 0.242 AC XY: 17692 AN XY: 73160

African (AFR) AF: 0.542 AC: 21944 AN: 40450

American (AMR) AF: 0.151 AC: 2264 AN: 15026

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 415 AN: 3452

East Asian (EAS) AF: 0.0555 AC: 285 AN: 5134

South Asian (SAS) AF: 0.0976 AC: 464 AN: 4756

European-Finnish (FIN) AF: 0.113 AC: 1164 AN: 10282

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10129 AN: 67640

Other (OTH) AF: 0.216 AC: 446 AN: 2068

Alfa AF: 0.163 Hom.: 2033

Bravo AF: 0.265

Asia WGS AF: 0.133 AC: 463 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.8
DANN	Benign	0.74
PhyloP100		0.13
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: rs7530361; hg19: chr1-100462860;