rs61749869

Variant names:

• chr17-34983476-C-A
• rs61749869
• NM_013975.4:c.471C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-34983476-C-A
• chr17-34983476-C-G
• chr17-34983476-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_013975.4(LIG3):​c.471C>A​(p.Ile157Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,614,020 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: LIG3 NM_013975.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.71
• Publications: 3 publications found

Genes affected

LIG3 (HGNC:6600): (DNA ligase 3) This gene is a member of the DNA ligase family. Each member of this family encodes a protein that catalyzes the joining of DNA ends but they each have a distinct role in DNA metabolism. The protein encoded by this gene is involved in excision repair and is located in both the mitochondria and nucleus, with translation initiation from the upstream start codon allowing for transport to the mitochondria and translation initiation from a downstream start codon allowing for transport to the nucleus. Additionally, alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

LIG3 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 20 (mngie type)

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 17-34983476-C-A is Benign according to our data. Variant chr17-34983476-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 632876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.71 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00131 (200/152200) while in subpopulation NFE AF = 0.00209 (142/68020). AF 95% confidence interval is 0.00181. There are 0 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013975.4. 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
	LIG3	NM_013975.4	MANE Select	c.471C>A	p.Ile157Ile	synonymous	Exon 2 of 20	NP_039269.2	P49916-1
	LIG3	NM_002311.5		c.471C>A	p.Ile157Ile	synonymous	Exon 2 of 20	NP_002302.2	P49916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG3	ENST00000378526.9	TSL:1 MANE Select	c.471C>A	p.Ile157Ile	synonymous	Exon 2 of 20	ENSP00000367787.3	P49916-1
	LIG3	ENST00000262327.9	TSL:1	c.471C>A	p.Ile157Ile	synonymous	Exon 2 of 20	ENSP00000262327.4	P49916-2
	LIG3	ENST00000585941.5	TSL:1	c.498C>A	p.Ile166Ile	synonymous	Exon 2 of 9	ENSP00000468479.1	K7ERZ5

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 200 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00209

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00108 AC: 271 AN: 250154 AF XY: 0.00109

Gnomad AFR exome AF: 0.000510

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00180

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00149 AC: 2179 AN: 1461820 Hom.: 2 Cov.: 34 AF XY: 0.00142 AC XY: 1035 AN XY: 727208

African (AFR) AF: 0.000299 AC: 10 AN: 33480

American (AMR) AF: 0.000179 AC: 8 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 89 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86232

European-Finnish (FIN) AF: 0.000842 AC: 45 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00173 AC: 1928 AN: 1111990

Other (OTH) AF: 0.00136 AC: 82 AN: 60390

GnomAD4 genome AF: 0.00131 AC: 200 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74428

African (AFR) AF: 0.000602 AC: 25 AN: 41506

American (AMR) AF: 0.000458 AC: 7 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

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

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.000944 AC: 10 AN: 10598

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

European-Non Finnish (NFE) AF: 0.00209 AC: 142 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00178 Hom.: 0

Bravo AF: 0.00121

EpiCase AF: 0.00191

EpiControl AF: 0.00231

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	0.26
DANN	Benign	0.78
PhyloP100		-3.7
Mutation Taster		=91/9	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: rs61749869; hg19: chr17-33310495;