chr12-32744154-A-T

Position:

• chr12-32744154-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001278464.2(DNM1L):​c.*744A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,196 control chromosomes in the GnomAD database, including 1,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1904 hom., cov: 32)
  • Exomes 𝑓: 0.056 (0 hom.)
• Consequence: DNM1L NM_001278464.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.727

Genes affected

DNM1L (HGNC:2973): (dynamin 1 like) This gene encodes a member of the dynamin superfamily of GTPases. The encoded protein mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in this gene are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

YARS2 (HGNC:24249): (tyrosyl-tRNA synthetase 2) This gene encodes a mitochondrial protein that catalyzes the attachment of tyrosine to tRNA(Tyr). Mutations in this gene are associated with myopathy with lactic acidosis and sideroblastic anemia type 2 (MLASA2). [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 12-32744154-A-T is Benign according to our data. Variant chr12-32744154-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 308409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM1L	NM_001278464.2	c.*744A>T		3_prime_UTR_variant	21/21	ENST00000553257.6
DNM1L	NM_012062.5	c.*744A>T		3_prime_UTR_variant	20/20	ENST00000549701.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM1L	ENST00000549701.6	c.*744A>T		3_prime_UTR_variant	20/20	1	NM_012062.5
DNM1L	ENST00000553257.6	c.*744A>T		3_prime_UTR_variant	21/21	2	NM_001278464.2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23358 AN: 152060 Hom.: 1898 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.0556 AC: 1 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0625

GnomAD4 genome AF: 0.154 AC: 23377 AN: 152178 Hom.: 1904 Cov.: 32 AF XY: 0.151 AC XY: 11246 AN XY: 74414

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.167

Alfa AF: 0.0762 Hom.: 92

Bravo AF: 0.159

Asia WGS AF: 0.133 AC: 460 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Myopathy, lactic acidosis, and sideroblastic anemia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hereditary Sideroblastic Anemia with Myopathy and Lactic Acidosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.5
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs1971911; hg19: chr12-32897088;