Variant 7-87847942-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018843.4(SLC25A40):c.368C>T(p.Thr123Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00653 in 1,609,120 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 46 hom. )

Consequence

SLC25A40
NM_018843.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 9.83

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013886452).

BP6

Variant 7-87847942-G-A is Benign according to our data. Variant chr7-87847942-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657659.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A40	NM_018843.4 linkuse as main transcript	c.368C>T	p.Thr123Ile	missense_variant	7/12	ENST00000341119.10	NP_061331.2	Q8TBP6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC25A40	ENST00000341119.10 linkuse as main transcript	c.368C>T	p.Thr123Ile	missense_variant	7/12	1	NM_018843.4	ENSP00000344831.5	Q8TBP6
SLC25A40	ENST00000429674.5 linkuse as main transcript	n.*295C>T		non_coding_transcript_exon_variant	6/10	3		ENSP00000405566.1	F2Z3Q4
SLC25A40	ENST00000429674.5 linkuse as main transcript	n.*295C>T		3_prime_UTR_variant	6/10	3		ENSP00000405566.1	F2Z3Q4

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

756

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00604

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00831

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00540

AC:

1334

AN:

246890

Hom.:

AF XY:

0.00524

AC XY:

699

AN XY:

133400

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00102

Gnomad FIN exome

AF:

0.00783

Gnomad NFE exome

AF:

0.00888

Gnomad OTH exome

AF:

0.00466

GnomAD4 exome

AF:

0.00669

AC:

9750

AN:

1456906

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

4703

AN XY:

724516

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00113

Gnomad4 FIN exome

AF:

0.00820

Gnomad4 NFE exome

AF:

0.00788

Gnomad4 OTH exome

AF:

0.00503

GnomAD4 genome

AF:

0.00497

AC:

756

AN:

152214

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

375

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00604

Gnomad4 NFE

AF:

0.00831

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00744

Hom.:

Bravo

AF:

0.00445

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00584

AC:

709

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SLC25A40-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SLC25A40: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.076

MetaRNN

Benign

0.014

MetaSVM

Uncertain

-0.066

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.61

Sift

Uncertain

0.0070

Sift4G

Benign

0.15

Polyphen

0.77

Vest4

0.88

MVP

0.61

MPC

0.84

ClinPred

0.030

GERP RS

5.1

Varity_R

0.77

gMVP

0.50

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over