rs199887745

Positions:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1

The ENST00000628067.3(SLC25A22):​c.414C>T​(p.Ala138=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000182 in 1,546,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

SLC25A22
ENST00000628067.3 splice_region, synonymous

Scores

2
Splicing: ADA: 0.000009800
2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -2.91
Variant links:
Genes affected
SLC25A22 (HGNC:19954): (solute carrier family 25 member 22) This gene encodes a mitochondrial glutamate carrier. Mutations in this gene are associated with early infantile epileptic encephalopathy. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jul 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 11-792726-G-A is Benign according to our data. Variant chr11-792726-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 207151.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1, Likely_benign=2}.
BP7
Synonymous conserved (PhyloP=-2.91 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000189 (264/1394062) while in subpopulation MID AF= 0.00035 (2/5708). AF 95% confidence interval is 0.00019. There are 0 homozygotes in gnomad4_exome. There are 144 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC25A22NM_001191061.2 linkuse as main transcriptc.414C>T p.Ala138= splice_region_variant, synonymous_variant 7/10 ENST00000628067.3 NP_001177990.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC25A22ENST00000628067.3 linkuse as main transcriptc.414C>T p.Ala138= splice_region_variant, synonymous_variant 7/101 NM_001191061.2 ENSP00000486058 P1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000205
AC:
31
AN:
151098
Hom.:
0
AF XY:
0.000208
AC XY:
17
AN XY:
81786
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000239
Gnomad ASJ exome
AF:
0.000117
Gnomad EAS exome
AF:
0.000257
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000326
Gnomad OTH exome
AF:
0.000228
GnomAD4 exome
AF:
0.000189
AC:
264
AN:
1394062
Hom.:
0
Cov.:
33
AF XY:
0.000209
AC XY:
144
AN XY:
689004
show subpopulations
Gnomad4 AFR exome
AF:
0.000125
Gnomad4 AMR exome
AF:
0.000221
Gnomad4 ASJ exome
AF:
0.0000396
Gnomad4 EAS exome
AF:
0.0000826
Gnomad4 SAS exome
AF:
0.0000248
Gnomad4 FIN exome
AF:
0.0000796
Gnomad4 NFE exome
AF:
0.000213
Gnomad4 OTH exome
AF:
0.000189
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152154
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
8
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000270
Hom.:
0
Bravo
AF:
0.000106

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Oct 21, 2016- -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJan 09, 2015This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 03, 2018This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 07, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.030
DANN
Benign
0.71
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0000098
dbscSNV1_RF
Benign
0.0060
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199887745; hg19: chr11-792726; API