Variant 1-156200284-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014655.4(SLC25A44):c.437T>C(p.Met146Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Consequence

SLC25A44
NM_014655.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.11

Variant links:

Genes affected

SLC25A44 (HGNC:29036): (solute carrier family 25 member 44) SLC25A44 belongs to the SLC25 family of mitochondrial carrier proteins (Haitina et al., 2006 [PubMed 16949250]).[supplied by OMIM, Mar 2008]

SLC25A44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07048726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A44	NM_014655.4 link	c.437T>C	p.Met146Thr	missense_variant	2/4	ENST00000359511.5	NP_055470.1	Q96H78

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC25A44	ENST00000359511.5 link	c.437T>C	p.Met146Thr	missense_variant	2/4	1	NM_014655.4	ENSP00000352497.4	Q96H78
SLC25A44	ENST00000423538.6 link	c.437T>C	p.Met146Thr	missense_variant	2/4	1		ENSP00000407560.3	E9PGQ0
SLC25A44	ENST00000469537.1 link	n.4080T>C		non_coding_transcript_exon_variant	1/3	1
SLC25A44	ENST00000684582.1 link	c.114+6037T>C		intron_variant				ENSP00000507428.1	A0A804HJB0

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

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

Jan 04, 2022

The c.437T>C (p.M146T) alteration is located in exon 2 (coding exon 1) of the SLC25A44 gene. This alteration results from a T to C substitution at nucleotide position 437, causing the methionine (M) at amino acid position 146 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.083

.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.53

.;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.26

.;N

REVEL

Benign

0.18

Sift

Benign

0.60

.;T

Sift4G

Benign

0.60

T;T

Polyphen

0.0070

.;B

Vest4

0.20

MVP

0.48

MPC

0.79

ClinPred

0.097

GERP RS

3.3

Varity_R

0.053

gMVP

0.53

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