rs542602103

Variant names:

• chr12-98593707-C-G
• rs542602103
• NM_005888.4:c.-38C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-98593707-C-G
• chr12-98593707-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_002635.4(SLC25A3):​c.-38C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 552,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: SLC25A3 NM_002635.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.948
• Publications: 0 publications found

Genes affected

SLC25A3 (HGNC:10989): (solute carrier family 25 member 3) The protein encoded by this gene catalyzes the transport of phosphate into the mitochondrial matrix, either by proton cotransport or in exchange for hydroxyl ions. The protein contains three related segments arranged in tandem which are related to those found in other characterized members of the mitochondrial carrier family. Both the N-terminal and C-terminal regions of this protein protrude toward the cytosol. Multiple alternatively spliced transcript variants have been isolated. [provided by RefSeq, Jul 2008]

SLC25A3 Gene-Disease associations (from GenCC):

• cardiomyopathy-hypotonia-lactic acidosis syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 12-98593707-C-G is Benign according to our data. Variant chr12-98593707-C-G is described in ClinVar as Benign. ClinVar VariationId is 139150.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0019 (289/152354) while in subpopulation AFR AF = 0.00618 (257/41588). AF 95% confidence interval is 0.00556. There are 0 homozygotes in GnomAd4. There are 133 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002635.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A3	NM_005888.4	MANE Plus Clinical	c.-38C>G		5_prime_UTR	Exon 1 of 8	NP_005879.1	Q00325-1
	SLC25A3	NM_002635.4	MANE Select	c.-38C>G		5_prime_UTR	Exon 1 of 8	NP_002626.1	A0A024RBE8
	SLC25A3	NM_213611.3		c.-272C>G		5_prime_UTR	Exon 1 of 7	NP_998776.1	Q00325-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC25A3	ENST00000228318.8	TSL:5 MANE Plus Clinical	c.-38C>G		5_prime_UTR	Exon 1 of 8	ENSP00000228318.3	Q00325-1
	SLC25A3	ENST00000552981.6	TSL:1 MANE Select	c.-38C>G		5_prime_UTR	Exon 1 of 8	ENSP00000448708.2	Q00325-2
	SLC25A3	ENST00000188376.9	TSL:1	c.-272C>G		5_prime_UTR	Exon 1 of 7	ENSP00000188376.5	Q00325-2

Frequencies

GnomAD3 genomes AF: 0.00190 AC: 289 AN: 152236 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

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: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000272 AC: 109 AN: 400644 Hom.: 0 Cov.: 0 AF XY: 0.000232 AC XY: 49 AN XY: 211242

African (AFR) AF: 0.00552 AC: 63 AN: 11420

American (AMR) AF: 0.000819 AC: 14 AN: 17084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12442

East Asian (EAS) AF: 0.00 AC: 0 AN: 26764

South Asian (SAS) AF: 0.00 AC: 0 AN: 44606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1722

European-Non Finnish (NFE) AF: 0.0000796 AC: 19 AN: 238820

Other (OTH) AF: 0.000559 AC: 13 AN: 23238

GnomAD4 genome AF: 0.00190 AC: 289 AN: 152354 Hom.: 0 Cov.: 33 AF XY: 0.00179 AC XY: 133 AN XY: 74498

African (AFR) AF: 0.00618 AC: 257 AN: 41588

American (AMR) AF: 0.00144 AC: 22 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00233

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.3
DANN	Benign	0.89
PhyloP100		-0.95
PromoterAI		0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs542602103; hg19: chr12-98987485;