rs1553205151

Variant names:

• chr1-100022457-G-A
• rs1553205151
• NM_012243.3:c.959G>A
• SLC35A3 p.Gly320Glu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012243.3(SLC35A3):​c.959G>A​(p.Gly320Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,441,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: SLC35A3 NM_012243.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 3.95
• 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: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000283761 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11828184).

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.959G>A	p.Gly320Glu	missense	Exon 8 of 8	NP_036375.1	Q9Y2D2-1
	SLC35A3	NM_001271685.2		c.1085G>A	p.Gly362Glu	missense	Exon 8 of 8	NP_001258614.1	Q9Y2D2-2
	SLC35A3	NM_001438725.1		c.959G>A	p.Gly320Glu	missense	Exon 9 of 9	NP_001425654.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A3	ENST00000533028.8	TSL:1 MANE Select	c.959G>A	p.Gly320Glu	missense	Exon 8 of 8	ENSP00000433849.1	Q9Y2D2-1
	SLC35A3	ENST00000638336.1	TSL:1	c.*43G>A		3_prime_UTR	Exon 6 of 6	ENSP00000491145.1	Q9Y2D2-3
	ENSG00000283761	ENST00000639037.1	TSL:5	c.753+7037G>A		intron	N/A	ENSP00000492745.1	A0A1W2PSA9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1441614 Hom.: 0 Cov.: 25 AF XY: 0.00000418 AC XY: 3 AN XY: 718458

African (AFR) AF: 0.00 AC: 0 AN: 32948

American (AMR) AF: 0.0000226 AC: 1 AN: 44152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39448

South Asian (SAS) AF: 0.00 AC: 0 AN: 85122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1095202

Other (OTH) AF: 0.00 AC: 0 AN: 59668

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000611 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	2	-	Autism spectrum disorder - epilepsy - arthrogryposis syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0045	T
Eigen	Benign	0.028
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.9
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.10
Sift	Benign	0.86	T
Sift4G	Benign	1.0	T
Varity_R		0.12
gMVP		0.61
Mutation Taster		=77/23	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1553205151;

hg19: chr1-100488013;

COSMIC: COSV64516547;

COSMIC: COSV64516547;