8-23529093-A-T

Position:

• chr8-23529093-A-T

Variant summary

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

The NM_016612.4(SLC25A37):​c.91A>T​(p.Thr31Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC25A37 NM_016612.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0420

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=0.095448524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A37	NM_016612.4	c.91A>T	p.Thr31Ser	missense_variant	1/4	ENST00000519973.6	NP_057696.2
SLC25A37	NM_001317812.2	c.-840A>T		5_prime_UTR_variant	1/4		NP_001304741.1
SLC25A37	NM_001317813.2	c.-250A>T		5_prime_UTR_variant	1/5		NP_001304742.1
SLC25A37	NM_001317814.2	c.-197A>T		5_prime_UTR_variant	1/5		NP_001304743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A37	ENST00000519973.6	c.91A>T	p.Thr31Ser	missense_variant	1/4	1	NM_016612.4	ENSP00000429200	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Aug 15, 2023

The c.91A>T (p.T31S) alteration is located in exon 1 (coding exon 1) of the SLC25A37 gene. This alteration results from a A to T substitution at nucleotide position 91, causing the threonine (T) at amino acid position 31 to be replaced by a serine (S). 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	0.069
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.3
DANN	Benign	0.91
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	0.99	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.14	N;N
REVEL	Benign	0.20
Sift	Benign	0.72	T;T
Sift4G	Benign	0.80	T;T
Polyphen		0.0010	B;.
Vest4		0.15
MutPred		0.25		Gain of helix (P = 0.0425);.;
MVP		0.55
MPC		0.35
ClinPred		0.060	T
GERP RS		3.6
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.046
gMVP		0.16

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: chr8-23386606;