8-23529123-A-C

Position:

• chr8-23529123-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016612.4(SLC25A37):​c.121A>C​(p.Thr41Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC25A37 NM_016612.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22

Genes affected

SLC25A37 (HGNC:29786): (solute carrier family 25 member 37) SLC25A37 is a solute carrier localized in the mitochondrial inner membrane. It functions as an essential iron importer for the synthesis of mitochondrial heme and iron-sulfur clusters (summary by Chen et al., 2009 [PubMed 19805291]).[supplied by OMIM, Jan 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12001255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A37	NM_016612.4	c.121A>C	p.Thr41Pro	missense_variant	1/4	ENST00000519973.6	NP_057696.2
SLC25A37	NM_001317813.2	c.-220A>C		5_prime_UTR_variant	1/5		NP_001304742.1
SLC25A37	NM_001317814.2	c.-167A>C		5_prime_UTR_variant	1/5		NP_001304743.1
SLC25A37	NM_001317812.2	c.-810A>C		5_prime_UTR_variant	1/4		NP_001304741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A37	ENST00000519973.6	c.121A>C	p.Thr41Pro	missense_variant	1/4	1	NM_016612.4	ENSP00000429200.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458988 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2024

The c.121A>C (p.T41P) alteration is located in exon 1 (coding exon 1) of the SLC25A37 gene. This alteration results from a A to C substitution at nucleotide position 121, causing the threonine (T) at amino acid position 41 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.80
DEOGEN2	Benign	0.33	T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.76	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.25
Sift	Benign	0.54	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.0090	B;.
Vest4		0.15
MutPred		0.17		Loss of glycosylation at T41 (P = 0.033);.;
MVP		0.44
MPC		0.51
ClinPred		0.34	T
GERP RS		3.3
Varity_R		0.40
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-23386636;