chr1-99993465-C-T

Position:

• chr1-99993465-C-T

Variant summary

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

The ENST00000533028.8(SLC35A3):​c.-18-72C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0468 in 1,263,828 control chromosomes in the GnomAD database, including 1,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (346 hom., cov: 31)
  • Exomes 𝑓: 0.045 (1337 hom.)
• Consequence: SLC35A3 ENST00000533028.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06

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 (BayesDel_noAF=-0.83).
• BP6: Variant 1-99993465-C-T is Benign according to our data. Variant chr1-99993465-C-T is described in ClinVar as [Benign]. Clinvar id is 1234806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35A3	NM_012243.3	c.-18-72C>T		intron_variant		ENST00000533028.8	NP_036375.1
LOC124904230	XR_007066249.1	n.279+44265G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A3	ENST00000533028.8	c.-18-72C>T		intron_variant		1	NM_012243.3	ENSP00000433849	P1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 8920 AN: 150442 Hom.: 347 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0139

Gnomad EAS AF: 0.0151

Gnomad SAS AF: 0.0513

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0514

GnomAD4 exome AF: 0.0451 AC: 50204 AN: 1113268 Hom.: 1337 AF XY: 0.0453 AC XY: 25339 AN XY: 559460

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0227

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.0347

Gnomad4 SAS exome AF: 0.0513

Gnomad4 FIN exome AF: 0.0409

Gnomad4 NFE exome AF: 0.0450

Gnomad4 OTH exome AF: 0.0433

GnomAD4 genome AF: 0.0592 AC: 8920 AN: 150560 Hom.: 346 Cov.: 31 AF XY: 0.0586 AC XY: 4311 AN XY: 73504

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0362

Gnomad4 ASJ AF: 0.0139

Gnomad4 EAS AF: 0.0151

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.0409

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0499

Alfa AF: 0.0587 Hom.: 44

Bravo AF: 0.0581

Asia WGS AF: 0.0350 AC: 122 AN: 3478

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	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.64

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: rs74647865; hg19: chr1-100459021;