rs74102304

Variant names:

• chr1-99993576-G-A
• rs74102304
• NM_012243.3:c.22G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001271685.2(SLC35A3):​c.148G>A​(p.Val50Ile) 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. 15/21 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_001271685.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.914
• Publications: 8 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271685.2. 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.22G>A	p.Val8Ile	missense	Exon 2 of 8	NP_036375.1
	SLC35A3	NM_001271685.2		c.148G>A	p.Val50Ile	missense	Exon 2 of 8	NP_001258614.1
	SLC35A3	NM_001438725.1		c.22G>A	p.Val8Ile	missense	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.22G>A	p.Val8Ile	missense	Exon 2 of 8	ENSP00000433849.1
	ENSG00000283761	ENST00000639037.1	TSL:5	c.22G>A	p.Val8Ile	missense	Exon 2 of 17	ENSP00000492745.1
	SLC35A3	ENST00000638336.1	TSL:1	c.22G>A	p.Val8Ile	missense	Exon 2 of 6	ENSP00000491145.1

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

GnomAD2 exomes AF: 0.00861 AC: 2164 AN: 251286 AF XY: 0.00662

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 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

African (AFR) AF: 0.115 AC: 3862 AN: 33460

American (AMR) AF: 0.00606 AC: 271 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00218 AC: 57 AN: 26128

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39656

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86244

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53414

Middle Eastern (MID) AF: 0.0120 AC: 69 AN: 5768

European-Non Finnish (NFE) AF: 0.000413 AC: 459 AN: 1111890

Other (OTH) AF: 0.00883 AC: 533 AN: 60382

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

African (AFR) AF: 0.111 AC: 4608 AN: 41420

American (AMR) AF: 0.0122 AC: 186 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4800

European-Finnish (FIN) AF: 0.0000949 AC: 1 AN: 10534

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 67972

Other (OTH) AF: 0.0204 AC: 43 AN: 2108

Alfa AF: 0.0118 Hom.: 176

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Arthrogryposis multiplex congenita (1)
-	-	1	Autism spectrum disorder - epilepsy - arthrogryposis syndrome (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.11	N
PhyloP100		0.91
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.039
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.040
ClinPred		0.0028	T
GERP RS		3.6
Varity_R		0.021
gMVP		0.074
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs74102304; hg19: chr1-100459132;