rs74102304

chr1-99993576-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012243.3(SLC35A3):c.22G>A(p.Val8Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00632 in 1,613,610 control chromosomes in the GnomAD database, including 514 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (283 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (231 hom.)
• Consequence: SLC35A3 NM_012243.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.914

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001616776).
• BP6: Variant 1-99993576-G-A is Benign according to our data. Variant chr1-99993576-G-A is described in ClinVar as [Benign]. Clinvar id is 474760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35A3	NM_012243.3	c.22G>A	p.Val8Ile	missense_variant	2/8	ENST00000533028.8
LOC124904230	XR_007066249.1	n.279+44154C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35A3	ENST00000533028.8	c.22G>A	p.Val8Ile	missense_variant	2/8	1	NM_012243.3	P1

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4880 AN: 151836 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.00861 AC: 2164 AN: 251286 Hom.: 92 AF XY: 0.00662 AC XY: 899 AN XY: 135810

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.00570

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000642

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00363 AC: 5304 AN: 1461656 Hom.: 231 Cov.: 31 AF XY: 0.00322 AC XY: 2343 AN XY: 727132

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.00606

Gnomad4 ASJ exome AF: 0.00218

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.000522

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.000413

Gnomad4 OTH exome AF: 0.00883

GnomAD4 genome AF: 0.0322 AC: 4897 AN: 151954 Hom.: 283 Cov.: 32 AF XY: 0.0313 AC XY: 2324 AN XY: 74280

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0000949

Gnomad4 NFE AF: 0.000588

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.00616 Hom.: 57

Bravo AF: 0.0361

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.117 AC: 517

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0111 AC: 1345

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Autism spectrum disorder - epilepsy - arthrogryposis syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 20, 2020

- -

Arthrogryposis multiplex congenita Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.86
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.89	D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaRNN	Benign	0.0016	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.45	T
Polyphen		0.0	.;B;B;.;.;.;.;B;.;.;.;.;.;.;.;.
Vest4		0.040, 0.052, 0.11
ClinPred		0.0028	T
GERP RS		3.6
Varity_R		0.021
gMVP		0.074

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: rs74102304; hg19: chr1-100459132;