1-99970577-A-G

Position:

• chr1-99970577-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012243.3(SLC35A3):​c.-19+415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,535,706 control chromosomes in the GnomAD database, including 1,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (152 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1373 hom.)
• Consequence: SLC35A3 NM_012243.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.485

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=0.0020925999).
• BP6: Variant 1-99970577-A-G is Benign according to our data. Variant chr1-99970577-A-G is described in ClinVar as [Benign]. Clinvar id is 1185185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0432 (6569/152164) while in subpopulation AFR AF= 0.0505 (2097/41498). AF 95% confidence interval is 0.0487. There are 152 homozygotes in gnomad4. There are 3086 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 152 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35A3	NM_012243.3	c.-19+415A>G		intron_variant		ENST00000533028.8	NP_036375.1
LOC124904230	XR_007066249.1	n.280-30507T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A3	ENST00000533028.8	c.-19+415A>G		intron_variant		1	NM_012243.3	ENSP00000433849	P1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6542 AN: 152046 Hom.: 147 Cov.: 32

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0385

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0433

Gnomad OTH AF: 0.0504

GnomAD3 exomes AF: 0.0379 AC: 5192 AN: 136918 Hom.: 118 AF XY: 0.0378 AC XY: 2812 AN XY: 74446

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.0212

Gnomad ASJ exome AF: 0.0387

Gnomad EAS exome AF: 0.0383

Gnomad SAS exome AF: 0.0370

Gnomad FIN exome AF: 0.0251

Gnomad NFE exome AF: 0.0452

Gnomad OTH exome AF: 0.0424

GnomAD4 exome AF: 0.0428 AC: 59221 AN: 1383542 Hom.: 1373 Cov.: 30 AF XY: 0.0424 AC XY: 28956 AN XY: 682716

Gnomad4 AFR exome AF: 0.0486

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0405

Gnomad4 EAS exome AF: 0.0231

Gnomad4 SAS exome AF: 0.0359

Gnomad4 FIN exome AF: 0.0277

Gnomad4 NFE exome AF: 0.0450

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome AF: 0.0432 AC: 6569 AN: 152164 Hom.: 152 Cov.: 32 AF XY: 0.0415 AC XY: 3086 AN XY: 74402

Gnomad4 AFR AF: 0.0505

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.0410

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.0433

Gnomad4 OTH AF: 0.0499

Alfa AF: 0.0281 Hom.: 15

Bravo AF: 0.0449

TwinsUK AF: 0.0494 AC: 183

ALSPAC AF: 0.0457 AC: 176

ExAC AF: 0.0327 AC: 584

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SLC35A3-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Autism spectrum disorder - epilepsy - arthrogryposis syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.9
DANN	Uncertain	0.99
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.026
Sift	Benign	0.34	T
Sift4G	Benign	0.068	T
Polyphen		0.0	B
Vest4		0.041
ClinPred		0.011	T
GERP RS		0.61
gMVP		0.20

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: rs11166383; hg19: chr1-100436133;