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3-39383736-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_017875.4(SLC25A38):c.12C>T(p.Asn4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000689 in 1,614,194 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00069 ( 3 hom. )

Consequence

SLC25A38
NM_017875.4 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 1.31
Variant links:
Genes affected
SLC25A38 (HGNC:26054): (solute carrier family 25 member 38) This gene is a member of the mitochondrial carrier family. The encoded protein is required during erythropoiesis and is important for the biosynthesis of heme. Mutations in this gene are the cause of autosomal congenital sideroblastic anemia (anemia, sideroblastic, 2, pyridoxine-refractory). A related pseudogene is found on chromosome 1. [provided by RefSeq, Aug 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-39383736-C-T is Benign according to our data. Variant chr3-39383736-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 345143.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2, Benign=1}. Variant chr3-39383736-C-T is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.31 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000656 (100/152376) while in subpopulation AMR AF= 0.00104 (16/15312). AF 95% confidence interval is 0.000677. There are 0 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC25A38NM_017875.4 linkuse as main transcriptc.12C>T p.Asn4= synonymous_variant 1/7 ENST00000650617.1
LOC105377644XR_007096252.1 linkuse as main transcriptn.85+505G>A intron_variant, non_coding_transcript_variant
SLC25A38NM_001354798.2 linkuse as main transcriptc.12C>T p.Asn4= synonymous_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC25A38ENST00000650617.1 linkuse as main transcriptc.12C>T p.Asn4= synonymous_variant 1/7 NM_017875.4 P1
ENST00000655387.1 linkuse as main transcriptn.60+505G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000657
AC:
100
AN:
152258
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00105
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000853
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000801
AC:
201
AN:
250936
Hom.:
1
AF XY:
0.000877
AC XY:
119
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000868
Gnomad ASJ exome
AF:
0.00298
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000719
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.000953
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.000692
AC:
1012
AN:
1461818
Hom.:
3
Cov.:
30
AF XY:
0.000732
AC XY:
532
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000716
Gnomad4 ASJ exome
AF:
0.00268
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000881
Gnomad4 FIN exome
AF:
0.000112
Gnomad4 NFE exome
AF:
0.000647
Gnomad4 OTH exome
AF:
0.00114
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000656
AC:
100
AN:
152376
Hom.:
0
Cov.:
33
AF XY:
0.000698
AC XY:
52
AN XY:
74524
show subpopulations
Gnomad4 AFR
AF:
0.000192
Gnomad4 AMR
AF:
0.00104
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000853
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000914
Hom.:
0
Bravo
AF:
0.000691
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00174
EpiControl
AF:
0.00160

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 01, 2021- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 22, 2024- -
X-linked sideroblastic anemia 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Sideroblastic anemia 2 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
Cadd
Benign
10
Dann
Benign
0.79

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

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

Other links and lift over

dbSNP: rs142420345; hg19: chr3-39425227; API