17-44320716-T-G

Variant names:

• chr17-44320716-T-G
• NM_001143780.3:c.707A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001143780.3(SLC25A39):​c.707A>C​(p.Asn236Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC25A39 NM_001143780.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00
• Publications: 0 publications found

Genes affected

SLC25A39 (HGNC:24279): (solute carrier family 25 member 39) This gene encodes a member of the SLC25 transporter or mitochondrial carrier family of proteins. Members of this family are encoded by the nuclear genome while their protein products are usually embedded in the inner mitochondrial membrane and exhibit wide-ranging substrate specificity. Although the encoded protein is currently considered an orphan transporter, this protein is related to other carriers known to transport amino acids. This protein may play a role in iron homeostasis. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3934335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A39	NM_001143780.3	c.707A>C	p.Asn236Thr	missense_variant	Exon 9 of 12	ENST00000377095.10	NP_001137252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A39	ENST00000377095.10	c.707A>C	p.Asn236Thr	missense_variant	Exon 9 of 12	1	NM_001143780.3	ENSP00000366299.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.707A>C (p.N236T) alteration is located in exon 9 (coding exon 8) of the SLC25A39 gene. This alteration results from a A to C substitution at nucleotide position 707, causing the asparagine (N) at amino acid position 236 to be replaced by a threonine (T). 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	0.25
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	.;T;.;.;.;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	.;D;D;D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.39	T;T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.015	.;N;.;.;.;.
PhyloP100		6.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-4.2	D;D;.;.;D;.
REVEL	Uncertain	0.44
Sift	Benign	0.22	T;T;.;.;T;.
Sift4G	Benign	0.47	T;T;T;T;T;T
Polyphen		0.15	B;D;B;.;B;.
Vest4		0.75
MutPred		0.41		.;Gain of sheet (P = 0.1208);.;.;.;.;
MVP		0.69
MPC		0.057
ClinPred		0.96	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-42398084;