ENST00000940187.1:c.*2003G>A

Variant names:

• chr17-4935738-C-T
• rs2243100
• ENST00000940187.1:c.*2003G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000940187.1(SLC25A11):​c.*2003G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,218 control chromosomes in the GnomAD database, including 2,081 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2081 hom., cov: 32)
• Consequence: SLC25A11 ENST00000940187.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 12 publications found

Genes affected

SLC25A11 (HGNC:10981): (solute carrier family 25 member 11) The oxoglutarate/malate carrier transports 2-oxoglutarate across the inner membranes of mitochondria in an electroneutral exchange for malate or other dicarboxylic acids (summary by Iacobazzi et al., 1992 [PubMed 1457818]).[supplied by OMIM, Jan 2011]

SLC25A11 Gene-Disease associations (from GenCC):

• hereditary pheochromocytoma-paraganglioma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pheochromocytoma/paraganglioma syndrome 6

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000940187.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A11	ENST00000940187.1		c.*2003G>A		3_prime_UTR	Exon 7 of 7	ENSP00000610246.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24668 AN: 152100 Hom.: 2081 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24673 AN: 152218 Hom.: 2081 Cov.: 32 AF XY: 0.165 AC XY: 12266 AN XY: 74432

African (AFR) AF: 0.199 AC: 8254 AN: 41502

American (AMR) AF: 0.195 AC: 2989 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 387 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1305 AN: 5184

South Asian (SAS) AF: 0.129 AC: 621 AN: 4824

European-Finnish (FIN) AF: 0.186 AC: 1971 AN: 10614

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8717 AN: 68008

Other (OTH) AF: 0.133 AC: 282 AN: 2116

Alfa AF: 0.117 Hom.: 377

Bravo AF: 0.164

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.43
PhyloP100		-0.046

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2243100; hg19: chr17-4839033;