NM_017875.4:c.-303A>G

Variant names:

• chr3-39383422-A-G
• rs114422738
• NM_017875.4:c.-303A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017875.4(SLC25A38):​c.-303A>G 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 0.00000657 in 152,128 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC25A38 NM_017875.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.-303A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_060345.2	Q96DW6
	SLC25A38	NM_017875.4	MANE Select	c.-303A>G		5_prime_UTR	Exon 1 of 7	NP_060345.2	Q96DW6
	SLC25A38	NM_001354798.2		c.-303A>G		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.-303A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000497532.1	Q96DW6
	SLC25A38	ENST00000650617.1	MANE Select	c.-303A>G		5_prime_UTR	Exon 1 of 7	ENSP00000497532.1	Q96DW6
	SLC25A38	ENST00000949226.1		c.-303A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000619285.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 270828 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 143716

African (AFR) AF: 0.00 AC: 0 AN: 7962

American (AMR) AF: 0.00 AC: 0 AN: 12428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8040

East Asian (EAS) AF: 0.00 AC: 0 AN: 15272

South Asian (SAS) AF: 0.00 AC: 0 AN: 36504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 159542

Other (OTH) AF: 0.00 AC: 0 AN: 15254

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152128 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74324

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.5
DANN	Benign	0.51
PhyloP100		-0.38
PromoterAI		-0.0026	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: rs114422738; hg19: chr3-39424913;