12-32730998-C-T

Variant names:

• chr12-32730998-C-T
• rs184731250
• NM_001278464.2:c.1119-16C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_012062.5(DNM1L):​c.1080-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 1,613,590 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0071 (50 hom.)
• Consequence: DNM1L NM_012062.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.25

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 12-32730998-C-T is Benign according to our data. Variant chr12-32730998-C-T is described in ClinVar as [Benign]. Clinvar id is 260164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00642 (978/152246) while in subpopulation AMR AF = 0.0109 (166/15290). AF 95% confidence interval is 0.00951. There are 8 homozygotes in GnomAd4. There are 501 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1L	NM_001278464.2	c.1119-16C>T		intron_variant	Intron 10 of 20	ENST00000553257.6	NP_001265393.1
DNM1L	NM_012062.5	c.1080-16C>T		intron_variant	Intron 9 of 19	ENST00000549701.6	NP_036192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1L	ENST00000553257.6	c.1119-16C>T		intron_variant	Intron 10 of 20	2	NM_001278464.2	ENSP00000449089.1
DNM1L	ENST00000549701.6	c.1080-16C>T		intron_variant	Intron 9 of 19	1	NM_012062.5	ENSP00000450399.1

Frequencies

GnomAD3 genomes AF: 0.00644 AC: 979 AN: 152130 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0115

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00810

Gnomad OTH AF: 0.00815

GnomAD2 exomes AF: 0.00673 AC: 1691 AN: 251298 AF XY: 0.00686

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.00593

Gnomad ASJ exome AF: 0.0140

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0115

Gnomad NFE exome AF: 0.00839

Gnomad OTH exome AF: 0.00979

GnomAD4 exome AF: 0.00706 AC: 10317 AN: 1461344 Hom.: 50 Cov.: 32 AF XY: 0.00691 AC XY: 5026 AN XY: 726976

Gnomad4 AFR exome AF: 0.00134 AC: 45 AN: 33464

Gnomad4 AMR exome AF: 0.00602 AC: 269 AN: 44720

Gnomad4 ASJ exome AF: 0.0145 AC: 379 AN: 26122

Gnomad4 EAS exome AF: 0.0000505 AC: 2 AN: 39618

Gnomad4 SAS exome AF: 0.00217 AC: 187 AN: 86232

Gnomad4 FIN exome AF: 0.0117 AC: 625 AN: 53336

Gnomad4 NFE exome AF: 0.00751 AC: 8345 AN: 1111732

Gnomad4 Remaining exome AF: 0.00707 AC: 427 AN: 60364

GnomAD4 genome AF: 0.00642 AC: 978 AN: 152246 Hom.: 8 Cov.: 32 AF XY: 0.00673 AC XY: 501 AN XY: 74438

Gnomad4 AFR AF: 0.00164 AC: 0.00163666 AN: 0.00163666

Gnomad4 AMR AF: 0.0109 AC: 0.0108568 AN: 0.0108568

Gnomad4 ASJ AF: 0.0118 AC: 0.0118156 AN: 0.0118156

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00249 AC: 0.00248859 AN: 0.00248859

Gnomad4 FIN AF: 0.0115 AC: 0.0115051 AN: 0.0115051

Gnomad4 NFE AF: 0.00810 AC: 0.00810056 AN: 0.00810056

Gnomad4 OTH AF: 0.00807 AC: 0.00807217 AN: 0.00807217

Alfa AF: 0.00789 Hom.: 1

Bravo AF: 0.00559

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.85
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs184731250; hg19: chr12-32883932;