7-87843822-A-T

Position:

• chr7-87843822-A-T

Variant summary

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

The NM_018843.4(SLC25A40):​c.673T>A​(p.Cys225Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC25A40 NM_018843.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.95

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]

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.673T>A	p.Cys225Ser	missense_variant	9/12	ENST00000341119.10	NP_061331.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A40	ENST00000341119.10	c.673T>A	p.Cys225Ser	missense_variant	9/12	1	NM_018843.4	ENSP00000344831.5
SLC25A40	ENST00000446236.5	n.40T>A		non_coding_transcript_exon_variant	1/5	3		ENSP00000401473.1
SLC25A40	ENST00000429674.5	n.*559-2108T>A		intron_variant		3		ENSP00000405566.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458824 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725866

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: 0.00

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

Dec 03, 2021

The c.673T>A (p.C225S) alteration is located in exon 9 (coding exon 7) of the SLC25A40 gene. This alteration results from a T to A substitution at nucleotide position 673, causing the cysteine (C) at amino acid position 225 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	0.26
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Benign	0.81
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.70	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.43
Sift	Benign	0.53	T
Sift4G	Benign	0.45	T
Polyphen		0.12	B
Vest4		0.78
MutPred		0.43		Gain of disorder (P = 8e-04);
MVP		0.32
MPC		0.87
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.35
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1051889664; hg19: chr7-87473137;