rs1052536

Variant names:

• chr17-35004556-C-T
• rs1052536
• NM_013975.4:c.*50C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013975.4(LIG3):​c.*50C>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 0.432 in 1,480,518 control chromosomes in the GnomAD database, including 143,275 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11705 hom., cov: 31)
  • Exomes 𝑓: 0.44 (131570 hom.)
• Consequence: LIG3 NM_013975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 76 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

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.*50C>T		3_prime_UTR	Exon 20 of 20	NP_039269.2	P49916-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG3	ENST00000378526.9	TSL:1 MANE Select	c.*50C>T		3_prime_UTR	Exon 20 of 20	ENSP00000367787.3	P49916-1
	LIG3	ENST00000858902.1		c.*50C>T		3_prime_UTR	Exon 20 of 20	ENSP00000528961.1
	LIG3	ENST00000858903.1		c.*50C>T		3_prime_UTR	Exon 20 of 20	ENSP00000528962.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55521 AN: 151802 Hom.: 11707 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.377

GnomAD2 exomes AF: 0.417 AC: 100582 AN: 241450 AF XY: 0.420

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.304

Gnomad FIN exome AF: 0.570

Gnomad NFE exome AF: 0.464

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.439 AC: 583420 AN: 1328596 Hom.: 131570 Cov.: 19 AF XY: 0.438 AC XY: 290864 AN XY: 664474

African (AFR) AF: 0.141 AC: 4335 AN: 30702

American (AMR) AF: 0.409 AC: 17817 AN: 43612

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8440 AN: 24434

East Asian (EAS) AF: 0.241 AC: 9349 AN: 38824

South Asian (SAS) AF: 0.368 AC: 30330 AN: 82370

European-Finnish (FIN) AF: 0.566 AC: 29855 AN: 52740

Middle Eastern (MID) AF: 0.358 AC: 1957 AN: 5460

European-Non Finnish (NFE) AF: 0.460 AC: 457943 AN: 994754

Other (OTH) AF: 0.420 AC: 23394 AN: 55700

GnomAD4 genome AF: 0.365 AC: 55520 AN: 151922 Hom.: 11705 Cov.: 31 AF XY: 0.371 AC XY: 27526 AN XY: 74222

African (AFR) AF: 0.153 AC: 6335 AN: 41468

American (AMR) AF: 0.390 AC: 5951 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1171 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1476 AN: 5148

South Asian (SAS) AF: 0.364 AC: 1748 AN: 4808

European-Finnish (FIN) AF: 0.569 AC: 5990 AN: 10522

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31505 AN: 67930

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.412 Hom.: 28372

Bravo AF: 0.342

Asia WGS AF: 0.345 AC: 1197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		-0.084
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1052536; hg19: chr17-33331575; COSMIC: COSV52007077; COSMIC: COSV52007077;