1-100007096-A-T

Position:

• chr1-100007096-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012243.3(SLC35A3):​c.405A>T​(p.Lys135Asn) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35A3 NM_012243.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946

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]

LOC124904230 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3375278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A3	NM_012243.3	c.405A>T	p.Lys135Asn	missense_variant	4/8	ENST00000533028.8
LOC124904230	XR_007066249.1	n.279+30634T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A3	ENST00000533028.8	c.405A>T	p.Lys135Asn	missense_variant	4/8	1	NM_012243.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Uncertain	1.0
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	D;.;.;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.34	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Pathogenic	0.79	T
Polyphen		0.033	.;B;B;.;.;B;.;.;.;.;.;.;.
Vest4		0.42, 0.42, 0.46
MutPred		0.56		Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);.;Loss of methylation at K135 (P = 0.0289);Loss of methylation at K135 (P = 0.0289);
MVP		0.70
ClinPred		0.75	D
GERP RS		0.60
Varity_R		0.28
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs754559092; hg19: chr1-100472652;