8-23529093-A-T

Variant names:

• chr8-23529093-A-T
• NM_016612.4:c.91A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095448524).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016612.4. 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
	SLC25A37	NM_016612.4	MANE Select	c.91A>T	p.Thr31Ser	missense	Exon 1 of 4	NP_057696.2	Q9NYZ2-1
	SLC25A37	NM_001317813.2		c.-250A>T		5_prime_UTR	Exon 1 of 5	NP_001304742.1
	SLC25A37	NM_001317814.2		c.-197A>T		5_prime_UTR	Exon 1 of 5	NP_001304743.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A37	ENST00000519973.6	TSL:1 MANE Select	c.91A>T	p.Thr31Ser	missense	Exon 1 of 4	ENSP00000429200.1	Q9NYZ2-1
	SLC25A37	ENST00000290075.10	TSL:1	n.91A>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000290075.6	Q9NYZ2-2
	SLC25A37	ENST00000518881.5	TSL:1	n.127A>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.042
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.20
Sift	Benign	0.72	T
Sift4G	Benign	0.80	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
PromoterAI		-0.0039	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.046
gMVP		0.16
Mutation Taster		=89/11	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

hg19: chr8-23386606;