1-99993594-G-C

Variant names:

• chr1-99993594-G-C
• NM_012243.3:c.40G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012243.3(SLC35A3):​c.40G>C​(p.Val14Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V14I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC35A3 NM_012243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.44

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]

ENSG00000283761 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A3	NM_012243.3	c.40G>C	p.Val14Leu	missense_variant	Exon 2 of 8	ENST00000533028.8	NP_036375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A3	ENST00000533028.8	c.40G>C	p.Val14Leu	missense_variant	Exon 2 of 8	1	NM_012243.3	ENSP00000433849.1
ENSG00000283761	ENST00000639037.1	c.40G>C	p.Val14Leu	missense_variant	Exon 2 of 17	5		ENSP00000492745.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;T;T;.;.;.;.;T;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.79	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	3.5	.;H;H;.;H;.;.;H;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.0	.;.;N;.;.;.;.;N;.;.;.;.;.;N;.;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.019	.;.;D;.;.;.;.;D;.;.;.;.;.;D;.;.
Sift4G	Benign	0.070	.;T;T;.;.;.;.;T;.;.;.;.;.;T;.;.
Polyphen		0.086	.;B;B;.;.;.;.;B;.;.;.;.;.;.;.;.
Vest4		0.73, 0.72, 0.70
MutPred		0.69		Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);.;Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);
MVP		0.73
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.70
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-100459150;