Variant 7-87854214-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018843.4(SLC25A40):c.254A>G(p.Gln85Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC25A40
NM_018843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08506742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A40	NM_018843.4 linkuse as main transcript	c.254A>G	p.Gln85Arg	missense_variant	5/12	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.254A>G	p.Gln85Arg	missense_variant	5/12	1	NM_018843.4	ENSP00000344831.5	Q8TBP6
SLC25A40	ENST00000429674.5 linkuse as main transcript	n.*181A>G		non_coding_transcript_exon_variant	4/10	3		ENSP00000405566.1	F2Z3Q4
SLC25A40	ENST00000429674.5 linkuse as main transcript	n.*181A>G		3_prime_UTR_variant	4/10	3		ENSP00000405566.1	F2Z3Q4
SLC25A40	ENST00000444363.5 linkuse as main transcript	n.*181A>G		downstream_gene_variant		3		ENSP00000407780.1	F2Z3Q4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152196

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454482

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724208

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.254A>G (p.Q85R) alteration is located in exon 5 (coding exon 3) of the SLC25A40 gene. This alteration results from a A to G substitution at nucleotide position 254, causing the glutamine (Q) at amino acid position 85 to be replaced by an arginine (R). 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

0.051

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.057

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.77

M_CAP

Benign

0.011

MetaRNN

Benign

0.085

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.67

PrimateAI

Benign

0.22

PROVEAN

Benign

0.060

REVEL

Benign

0.27

Sift

Benign

0.53

Sift4G

Benign

0.93

Polyphen

0.0

Vest4

0.11

MutPred

0.53

Gain of MoRF binding (P = 0.0252);

MVP

0.13

MPC

0.24

ClinPred

0.015

GERP RS

-0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.068

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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