rs184769974

Variant names:

• chr3-39383452-G-A
• rs184769974
• NM_017875.4:c.-273G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-39383452-G-A
• chr3-39383452-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017875.4(SLC25A38):​c.-273G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 513,966 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00053 (2 hom.)
• Consequence: SLC25A38 NM_017875.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.34
• Publications: 1 publications found

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]

SLC25A38 Gene-Disease associations (from GenCC):

• sideroblastic anemia 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal recessive sideroblastic anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287780 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-39383452-G-A is Benign according to our data. Variant chr3-39383452-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 901070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00422 (643/152370) while in subpopulation AFR AF = 0.0146 (609/41592). AF 95% confidence interval is 0.0137. There are 4 homozygotes in GnomAd4. There are 295 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017875.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A38	NM_017875.4	MANE Select	c.-273G>A		5_prime_UTR	Exon 1 of 7	NP_060345.2	Q96DW6
	SLC25A38	NM_001354798.2		c.-273G>A		5_prime_UTR	Exon 1 of 6	NP_001341727.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A38	ENST00000650617.1	MANE Select	c.-273G>A		5_prime_UTR	Exon 1 of 7	ENSP00000497532.1	Q96DW6
	SLC25A38	ENST00000949226.1		c.-273G>A		5_prime_UTR	Exon 1 of 8	ENSP00000619285.1
	SLC25A38	ENST00000885742.1		c.-273G>A		5_prime_UTR	Exon 1 of 7	ENSP00000555801.1

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 641 AN: 152252 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

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: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000531 AC: 192 AN: 361596 Hom.: 2 Cov.: 0 AF XY: 0.000463 AC XY: 89 AN XY: 192310

African (AFR) AF: 0.0143 AC: 147 AN: 10260

American (AMR) AF: 0.00134 AC: 21 AN: 15702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10842

East Asian (EAS) AF: 0.00 AC: 0 AN: 22680

South Asian (SAS) AF: 0.0000456 AC: 2 AN: 43894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1546

European-Non Finnish (NFE) AF: 0.0000233 AC: 5 AN: 214906

Other (OTH) AF: 0.000827 AC: 17 AN: 20562

GnomAD4 genome AF: 0.00422 AC: 643 AN: 152370 Hom.: 4 Cov.: 33 AF XY: 0.00396 AC XY: 295 AN XY: 74512

African (AFR) AF: 0.0146 AC: 609 AN: 41592

American (AMR) AF: 0.00170 AC: 26 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.0000699 Hom.: 0

Bravo AF: 0.00491

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Sideroblastic anemia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		1.3
PromoterAI		0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs184769974; hg19: chr3-39424943;