rs114422738

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-39383422-A-C
• chr3-39383422-A-G

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.-303A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 423,062 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (42 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (9 hom.)
• Consequence: SLC25A38 NM_017875.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-39383422-A-C is Benign according to our data. Variant chr3-39383422-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 345134.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 = 0.0127 (1930/152242) while in subpopulation AFR AF = 0.0439 (1823/41556). AF 95% confidence interval is 0.0422. There are 42 homozygotes in GnomAd4. There are 909 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 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.-303A>C		5_prime_UTR	Exon 1 of 7	NP_060345.2	Q96DW6
	SLC25A38	NM_001354798.2		c.-303A>C		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.-303A>C		5_prime_UTR	Exon 1 of 7	ENSP00000497532.1	Q96DW6
	SLC25A38	ENST00000949226.1		c.-303A>C		5_prime_UTR	Exon 1 of 8	ENSP00000619285.1
	SLC25A38	ENST00000885742.1		c.-303A>C		5_prime_UTR	Exon 1 of 7	ENSP00000555801.1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1923 AN: 152124 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

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: 0.0000882

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00161 AC: 436 AN: 270820 Hom.: 9 Cov.: 0 AF XY: 0.00143 AC XY: 205 AN XY: 143710

African (AFR) AF: 0.0425 AC: 338 AN: 7954

American (AMR) AF: 0.00306 AC: 38 AN: 12428

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

East Asian (EAS) AF: 0.0000655 AC: 1 AN: 15272

South Asian (SAS) AF: 0.000137 AC: 5 AN: 36504

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

Middle Eastern (MID) AF: 0.000879 AC: 1 AN: 1138

European-Non Finnish (NFE) AF: 0.0000627 AC: 10 AN: 159542

Other (OTH) AF: 0.00282 AC: 43 AN: 15254

GnomAD4 genome AF: 0.0127 AC: 1930 AN: 152242 Hom.: 42 Cov.: 33 AF XY: 0.0122 AC XY: 909 AN XY: 74450

African (AFR) AF: 0.0439 AC: 1823 AN: 41556

American (AMR) AF: 0.00484 AC: 74 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

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

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67996

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00364 Hom.: 3

Bravo AF: 0.0147

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.53
PhyloP100		-0.38
PromoterAI		0.050	Neutral
Mutation Taster		=300/0	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: rs114422738; hg19: chr3-39424913;