NM_012243.3:c.63T>C

Variant names:

• chr1-99993617-T-C
• rs141542767
• NM_012243.3:c.63T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012243.3(SLC35A3):​c.63T>C​(p.Val21Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V21V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35A3 NM_012243.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315
• 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

ENSG00000283761 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.315 with no splicing effect.

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.63T>C	p.Val21Val	synonymous	Exon 2 of 8	NP_036375.1
	SLC35A3	NM_001271685.2		c.189T>C	p.Val63Val	synonymous	Exon 2 of 8	NP_001258614.1
	SLC35A3	NM_001438725.1		c.63T>C	p.Val21Val	synonymous	Exon 3 of 9	NP_001425654.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A3	ENST00000533028.8	TSL:1 MANE Select	c.63T>C	p.Val21Val	synonymous	Exon 2 of 8	ENSP00000433849.1
	ENSG00000283761	ENST00000639037.1	TSL:5	c.63T>C	p.Val21Val	synonymous	Exon 2 of 17	ENSP00000492745.1
	SLC35A3	ENST00000638336.1	TSL:1	c.63T>C	p.Val21Val	synonymous	Exon 2 of 6	ENSP00000491145.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.7
DANN	Benign	0.82
PhyloP100		0.32
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs141542767; hg19: chr1-100459173;