7-107919466-G-C

Variant names:

• chr7-107919466-G-C
• rs4564
• NM_000108.5:c.*207G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000108.5(DLD):​c.*207G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DLD NM_000108.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 22 publications found

Genes affected

DLD (HGNC:2898): (dihydrolipoamide dehydrogenase) This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. In homodimeric form, the encoded protein functions as a dehydrogenase and is found in several multi-enzyme complexes that regulate energy metabolism. However, as a monomer, this protein can function as a protease. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

DLD Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• pyruvate dehydrogenase E3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000108.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLD	NM_000108.5	MANE Select	c.*207G>C		3_prime_UTR	Exon 14 of 14	NP_000099.2
	DLD	NM_001289751.1		c.*207G>C		3_prime_UTR	Exon 13 of 13	NP_001276680.1
	DLD	NM_001289752.1		c.*207G>C		3_prime_UTR	Exon 13 of 13	NP_001276681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLD	ENST00000205402.10	TSL:1 MANE Select	c.*207G>C		3_prime_UTR	Exon 14 of 14	ENSP00000205402.3
	DLD	ENST00000415325.5	TSL:2	n.*1411G>C		non_coding_transcript_exon	Exon 12 of 12	ENSP00000402593.1
	DLD	ENST00000440410.5	TSL:2	c.*207G>C		3_prime_UTR	Exon 13 of 13	ENSP00000417016.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 325786 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 174664

African (AFR) AF: 0.00 AC: 0 AN: 9850

American (AMR) AF: 0.00 AC: 0 AN: 12220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10134

East Asian (EAS) AF: 0.00 AC: 0 AN: 21490

South Asian (SAS) AF: 0.00 AC: 0 AN: 30972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1424

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 203818

Other (OTH) AF: 0.00 AC: 0 AN: 18904

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 14937

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.99
DANN	Benign	0.54
PhyloP100		-0.0090
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4564; hg19: chr7-107559911;