7-87841651-T-C

Position:

• chr7-87841651-T-C

Variant summary

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

The NM_018843.4(SLC25A40):​c.805A>G​(p.Thr269Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 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)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SLC25A40 NM_018843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99

Genes affected

SLC25A40 (HGNC:29680): (solute carrier family 25 member 40) SLC25A40 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

SLC25A40 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A40	NM_018843.4	c.805A>G	p.Thr269Ala	missense_variant	10/12	ENST00000341119.10	NP_061331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A40	ENST00000341119.10	c.805A>G	p.Thr269Ala	missense_variant	10/12	1	NM_018843.4	ENSP00000344831.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367740 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 675792

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: 9.39e-7

Gnomad4 OTH exome AF: 0.00

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

Jun 29, 2023

The c.805A>G (p.T269A) alteration is located in exon 10 (coding exon 8) of the SLC25A40 gene. This alteration results from a A to G substitution at nucleotide position 805, causing the threonine (T) at amino acid position 269 to be replaced by an alanine (A). 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	0.064
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.13	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.16
Sift	Benign	0.64	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.36		Loss of ubiquitination at K274 (P = 0.1);
MVP		0.31
MPC		0.24
ClinPred		0.56	D
GERP RS		4.6
Varity_R		0.031
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.34		Position offset: -18

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: chr7-87470966;