NM_130837.3:c.-144T>C

Variant names:

• chr3-193593234-T-C
• rs1057509207
• NM_130837.3:c.-144T>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_130837.3(OPA1):​c.-144T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000331 in 694,896 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: OPA1 NM_130837.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

OPA1 (HGNC:8140): (OPA1 mitochondrial dynamin like GTPase) The protein encoded by this gene is a nuclear-encoded mitochondrial protein with similarity to dynamin-related GTPases. The encoded protein localizes to the inner mitochondrial membrane and helps regulate mitochondrial stability and energy output. This protein also sequesters cytochrome c. Mutations in this gene have been associated with optic atrophy type 1, which is a dominantly inherited optic neuropathy resulting in progressive loss of visual acuity, leading in many cases to legal blindness. [provided by RefSeq, Aug 2017]

ATP13A4 (HGNC:25422): (ATPase 13A4) Predicted to enable ATPase-coupled cation transmembrane transporter activity. Predicted to be involved in cellular calcium ion homeostasis. Predicted to be located in endoplasmic reticulum membrane and endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293063 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130837.3. 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
	OPA1	NM_130837.3	MANE Select	c.-144T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 31	NP_570850.2	O60313-10
	OPA1	NM_130837.3	MANE Select	c.-144T>C		5_prime_UTR	Exon 1 of 31	NP_570850.2	O60313-10
	OPA1	NM_130836.3		c.-144T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 30	NP_570849.2	O60313-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPA1	ENST00000361510.8	TSL:5 MANE Select	c.-144T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 31	ENSP00000355324.2	O60313-10
	OPA1	ENST00000361908.8	TSL:1	c.-144T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 30	ENSP00000354681.3	O60313-2
	OPA1	ENST00000361510.8	TSL:5 MANE Select	c.-144T>C		5_prime_UTR	Exon 1 of 31	ENSP00000355324.2	O60313-10

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.0000221 AC: 12 AN: 542686 Hom.: 0 Cov.: 8 AF XY: 0.0000251 AC XY: 7 AN XY: 279264

African (AFR) AF: 0.000160 AC: 2 AN: 12522

American (AMR) AF: 0.00 AC: 0 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12990

East Asian (EAS) AF: 0.00 AC: 0 AN: 27144

South Asian (SAS) AF: 0.0000250 AC: 1 AN: 40004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2040

European-Non Finnish (NFE) AF: 0.0000217 AC: 8 AN: 368012

Other (OTH) AF: 0.0000360 AC: 1 AN: 27758

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74366

African (AFR) AF: 0.000169 AC: 7 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal dominant optic atrophy classic form (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		1.0
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=291/9	polymorphism

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: rs1057509207; hg19: chr3-193311023;