1-99993465-C-T

Variant names:

• chr1-99993465-C-T
• rs74647865
• NM_012243.3:c.-18-72C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012243.3(SLC35A3):​c.-18-72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 1,263,828 control chromosomes in the GnomAD database, including 1,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (346 hom., cov: 31)
  • Exomes 𝑓: 0.045 (1337 hom.)
• Consequence: SLC35A3 NM_012243.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-99993465-C-T is Benign according to our data. Variant chr1-99993465-C-T is described in ClinVar as Benign. ClinVar VariationId is 1234806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A3	NM_012243.3	MANE Select	c.-18-72C>T		intron	N/A	NP_036375.1	Q9Y2D2-1
	SLC35A3	NM_001271685.2		c.109-72C>T		intron	N/A	NP_001258614.1	Q9Y2D2-2
	SLC35A3	NM_001438725.1		c.-18-72C>T		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.-18-72C>T		intron	N/A	ENSP00000433849.1	Q9Y2D2-1
	ENSG00000283761	ENST00000639037.1	TSL:5	c.-18-72C>T		intron	N/A	ENSP00000492745.1	A0A1W2PSA9
	SLC35A3	ENST00000638336.1	TSL:1	c.-18-72C>T		intron	N/A	ENSP00000491145.1	Q9Y2D2-3

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 8920 AN: 150442 Hom.: 347 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0139

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0514

GnomAD4 exome AF: 0.0451 AC: 50204 AN: 1113268 Hom.: 1337 AF XY: 0.0453 AC XY: 25339 AN XY: 559460

African (AFR) AF: 0.108 AC: 2649 AN: 24502

American (AMR) AF: 0.0227 AC: 663 AN: 29206

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 363 AN: 21182

East Asian (EAS) AF: 0.0347 AC: 1222 AN: 35168

South Asian (SAS) AF: 0.0513 AC: 3484 AN: 67910

European-Finnish (FIN) AF: 0.0409 AC: 1764 AN: 43088

Middle Eastern (MID) AF: 0.0471 AC: 200 AN: 4248

European-Non Finnish (NFE) AF: 0.0450 AC: 37779 AN: 839914

Other (OTH) AF: 0.0433 AC: 2080 AN: 48050

GnomAD4 genome AF: 0.0592 AC: 8920 AN: 150560 Hom.: 346 Cov.: 31 AF XY: 0.0586 AC XY: 4311 AN XY: 73504

African (AFR) AF: 0.105 AC: 4307 AN: 40942

American (AMR) AF: 0.0362 AC: 547 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.0139 AC: 48 AN: 3456

East Asian (EAS) AF: 0.0151 AC: 77 AN: 5100

South Asian (SAS) AF: 0.0507 AC: 238 AN: 4694

European-Finnish (FIN) AF: 0.0409 AC: 421 AN: 10292

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0462 AC: 3127 AN: 67694

Other (OTH) AF: 0.0499 AC: 104 AN: 2086

Alfa AF: 0.0605 Hom.: 50

Bravo AF: 0.0581

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		1.1
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: rs74647865; hg19: chr1-100459021;