chr3-39383452-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_017875.4(SLC25A38):​c.-273G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000467 in 513,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: SLC25A38 NM_017875.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive sideroblastic anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287780 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000636 (23/361598) while in subpopulation EAS AF = 0.00101 (23/22680). AF 95% confidence interval is 0.000693. There are 0 homozygotes in GnomAdExome4. There are 9 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

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>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_060345.2	Q96DW6
	SLC25A38	NM_017875.4	MANE Select	c.-273G>T		5_prime_UTR	Exon 1 of 7	NP_060345.2	Q96DW6
	SLC25A38	NM_001354798.2		c.-273G>T		5_prime_UTR_premature_start_codon_gain	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>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000497532.1	Q96DW6
	SLC25A38	ENST00000650617.1	MANE Select	c.-273G>T		5_prime_UTR	Exon 1 of 7	ENSP00000497532.1	Q96DW6
	SLC25A38	ENST00000949226.1		c.-273G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000619285.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152252 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000636 AC: 23 AN: 361598 Hom.: 0 Cov.: 0 AF XY: 0.0000468 AC XY: 9 AN XY: 192312

African (AFR) AF: 0.00 AC: 0 AN: 10262

American (AMR) AF: 0.00 AC: 0 AN: 15702

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

East Asian (EAS) AF: 0.00101 AC: 23 AN: 22680

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 214906

Other (OTH) AF: 0.00 AC: 0 AN: 20562

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152252 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41470

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.86
PhyloP100		1.3
PromoterAI		-0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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;