rs139971743

Variant names:

• chrX-104104661-G-C
• rs139971743
• NM_001012755.5:c.597C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001012755.5(SLC25A53):​c.597C>G​(p.Ile199Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,209,807 control chromosomes in the GnomAD database, including 1 homozygotes. There are 541 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., 28 hem., cov: 23)
  • Exomes 𝑓: 0.0013 (1 hom. 513 hem.)
• Consequence: SLC25A53 NM_001012755.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.252
• Publications: 1 publications found

Genes affected

SLC25A53 (HGNC:31894): (solute carrier family 25 member 53) Predicted to be located in mitochondrial inner membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009632975).
• BS2: High Hemizygotes in GnomAd4 at 28 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012755.5. 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
	SLC25A53	NM_001012755.5	MANE Select	c.597C>G	p.Ile199Met	missense	Exon 2 of 2	NP_001012773.2	Q5H9E4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A53	ENST00000594199.3	TSL:1 MANE Select	c.597C>G	p.Ile199Met	missense	Exon 2 of 2	ENSP00000468980.1	Q5H9E4
	SLC25A53	ENST00000905741.1		c.597C>G	p.Ile199Met	missense	Exon 3 of 3	ENSP00000575800.1
	SLC25A53	ENST00000905742.1		c.597C>G	p.Ile199Met	missense	Exon 3 of 3	ENSP00000575801.1

Frequencies

GnomAD3 genomes AF: 0.00101 AC: 113 AN: 111559 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000979

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.00104

Gnomad ASJ AF: 0.00226

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000755

Gnomad FIN AF: 0.000166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00164

Gnomad OTH AF: 0.00133

GnomAD2 exomes AF: 0.00111 AC: 203 AN: 183084 AF XY: 0.00127

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000547

Gnomad ASJ exome AF: 0.00549

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.00157

Gnomad OTH exome AF: 0.00111

GnomAD4 exome AF: 0.00135 AC: 1482 AN: 1098192 Hom.: 1 Cov.: 31 AF XY: 0.00141 AC XY: 513 AN XY: 363550

African (AFR) AF: 0.0000379 AC: 1 AN: 26400

American (AMR) AF: 0.000767 AC: 27 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00511 AC: 99 AN: 19385

East Asian (EAS) AF: 0.0000662 AC: 2 AN: 30206

South Asian (SAS) AF: 0.000609 AC: 33 AN: 54148

European-Finnish (FIN) AF: 0.000271 AC: 11 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00149 AC: 1251 AN: 842086

Other (OTH) AF: 0.00126 AC: 58 AN: 46096

GnomAD4 genome AF: 0.00101 AC: 113 AN: 111615 Hom.: 0 Cov.: 23 AF XY: 0.000828 AC XY: 28 AN XY: 33811

African (AFR) AF: 0.0000977 AC: 3 AN: 30720

American (AMR) AF: 0.00104 AC: 11 AN: 10619

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 6 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3539

South Asian (SAS) AF: 0.000756 AC: 2 AN: 2645

European-Finnish (FIN) AF: 0.000166 AC: 1 AN: 6018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00164 AC: 87 AN: 52997

Other (OTH) AF: 0.00131 AC: 2 AN: 1526

Alfa AF: 0.00200 Hom.: 15

Bravo AF: 0.00127

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00138 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00238 AC: 16

ExAC AF: 0.00105 AC: 128

EpiCase AF: 0.00251

EpiControl AF: 0.00154

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	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.25
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.15	T
Polyphen		0.0060	B
Vest4		0.12
MVP		0.23
ClinPred		0.0096	T
GERP RS		3.2
Varity_R		0.21
gMVP		0.56

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

dbSNP: rs139971743; hg19: chrX-103349344;