1-99970124-C-T

Position:

• chr1-99970124-C-T

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.-57C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 156,290 control chromosomes in the GnomAD database, including 302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (299 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (3 hom.)
• Consequence: SLC35A3 NM_012243.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.553

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-99970124-C-T is Benign according to our data. Variant chr1-99970124-C-T is described in ClinVar as [Benign]. Clinvar id is 1287332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35A3	NM_012243.3	c.-57C>T		5_prime_UTR_variant	1/8	ENST00000533028.8	NP_036375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A3	ENST00000533028	c.-57C>T		5_prime_UTR_variant	1/8	1	NM_012243.3	ENSP00000433849.1
ENSG00000283761	ENST00000639037	c.-57C>T		5_prime_UTR_variant	1/17	5		ENSP00000492745.1

Frequencies

GnomAD3 genomes AF: 0.0331 AC: 5031 AN: 152132 Hom.: 298 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000603

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.00495 AC: 20 AN: 4044 Hom.: 3 Cov.: 0 AF XY: 0.00566 AC XY: 12 AN XY: 2120

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.00820

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: 0.00146

Gnomad4 OTH exome AF: 0.00699

GnomAD4 genome AF: 0.0331 AC: 5042 AN: 152246 Hom.: 299 Cov.: 32 AF XY: 0.0322 AC XY: 2395 AN XY: 74432

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.000800 Hom.: 1

Bravo AF: 0.0370

Asia WGS AF: 0.00953 AC: 34 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs111911110; hg19: chr1-100435680;