1-99993576-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
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
NM_012243.3 missense
Scores
1
11
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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: 4880AN: 151836Hom.: 282 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00861 AC: 2164AN: 251286Hom.: 92 AF XY: 0.00662 AC XY: 899AN XY: 135810
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GnomAD4 exome AF: 0.00363 AC: 5304AN: 1461656Hom.: 231 Cov.: 31 AF XY: 0.00322 AC XY: 2343AN XY: 727132
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GnomAD4 genome ? AF: 0.0322 AC: 4897AN: 151954Hom.: 283 Cov.: 32 AF XY: 0.0313 AC XY: 2324AN XY: 74280
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ESP6500AA
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517
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?
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1345
Asia WGS
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43
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3478
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
Polyphen
0.0
.;B;B;.;.;.;.;B;.;.;.;.;.;.;.;.
Vest4
0.040, 0.052, 0.11
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at