rs140707188

Variant names:

• chr1-156200071-G-A
• rs140707188
• NM_014655.4:c.224G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-156200071-G-A
• chr1-156200071-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014655.4(SLC25A44):​c.224G>A​(p.Arg75Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00097 in 1,614,110 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00052 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (1 hom.)
• Consequence: SLC25A44 NM_014655.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.74
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC25A44	NM_014655.4	c.224G>A	p.Arg75Gln	missense_variant	Exon 2 of 4	ENST00000359511.5	NP_055470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC25A44	ENST00000359511.5	c.224G>A	p.Arg75Gln	missense_variant	Exon 2 of 4	1	NM_014655.4	ENSP00000352497.4

Frequencies

GnomAD3 genomes AF: 0.000519 AC: 79 AN: 152116 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000450 AC: 113 AN: 251320 AF XY: 0.000398

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000827

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00102 AC: 1486 AN: 1461876 Hom.: 1 Cov.: 33 AF XY: 0.00101 AC XY: 736 AN XY: 727238

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00127 AC: 1413 AN: 1112004

Other (OTH) AF: 0.000878 AC: 53 AN: 60394

GnomAD4 genome AF: 0.000519 AC: 79 AN: 152234 Hom.: 1 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74428

African (AFR) AF: 0.000217 AC: 9 AN: 41556

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000985 AC: 67 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000794 Hom.: 1

Bravo AF: 0.000627

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.000428 AC: 52

EpiCase AF: 0.00104

EpiControl AF: 0.000889

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 09, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.224G>A (p.R75Q) alteration is located in exon 2 (coding exon 1) of the SLC25A44 gene. This alteration results from a G to A substitution at nucleotide position 224, causing the arginine (R) at amino acid position 75 to be replaced by a glutamine (Q). 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	0.18
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.34	.;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.9	.;L
PhyloP100		9.7
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.019	D;D
Polyphen		1.0	D;D
Vest4		0.88
MVP		0.74
MPC		1.8
ClinPred		0.29	T
GERP RS		5.0
Varity_R		0.48
gMVP		0.95
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs140707188; hg19: chr1-156169862;