rs886058665

Variant names:

• chr3-49021896-C-A
• rs886058665
• ENST00000451378.2:c.-95+112C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-49021896-C-A
• chr3-49021896-C-T

Variant summary

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

The NM_199070.2(NDUFAF3):​c.-95+112C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000245 in 408,078 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000025 (0 hom.)
• Consequence: NDUFAF3 NM_199070.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 0 publications found

Genes affected

NDUFAF3 (HGNC:29918): (NADH:ubiquinone oxidoreductase complex assembly factor 3) This gene encodes a mitochondrial complex I assembly protein that interacts with complex I subunits. Mutations in this gene cause mitochondrial complex I deficiency, a fatal neonatal disorder of the oxidative phosphorylation system. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2009]

DALRD3 (HGNC:25536): (DALR anticodon binding domain containing 3) The exact function of this gene is not known. It encodes a protein with a DALR anticodon binding domain similar to that of class Ia aminoacyl tRNA synthetases. This gene is located in a cluster of genes (with a complex sense-anti-sense genome architecture) on chromosome 3, and contains two micro RNA (miRNA) precursors (mir-425 and mir-191) in one of its introns. Preferential expression of this gene (the miRNAs and other genes in the cluster) in testis suggests a role of this gene in spermatogenesis (PMID:19906709). [provided by RefSeq, Feb 2013]

DALRD3 Gene-Disease associations (from GenCC):

• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• developmental and epileptic encephalopathy, 86

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae)

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=-0.62).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199070.2. 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
	NDUFAF3	NM_199070.2		c.-95+112C>A		intron	N/A	NP_951033.1	Q9BU61-2
	NDUFAF3	NM_199073.2		c.-94-450C>A		intron	N/A	NP_951047.1	Q9BU61-2
	NDUFAF3	NM_199074.2		c.-94-450C>A		intron	N/A	NP_951056.1	Q9BU61-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDUFAF3	ENST00000451378.2	TSL:1	c.-95+112C>A		intron	N/A	ENSP00000402465.2	Q9BU61-2
	NDUFAF3	ENST00000886525.1		c.-249C>A		5_prime_UTR	Exon 1 of 5	ENSP00000556584.1
	NDUFAF3	ENST00000326912.8	TSL:2	c.-94-450C>A		intron	N/A	ENSP00000323003.4	Q9BU61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000245 AC: 1 AN: 408078 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 214472

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 8630

American (AMR) AF: 0.00 AC: 0 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12356

East Asian (EAS) AF: 0.00 AC: 0 AN: 26530

South Asian (SAS) AF: 0.00 AC: 0 AN: 41574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1826

European-Non Finnish (NFE) AF: 0.00000401 AC: 1 AN: 249494

Other (OTH) AF: 0.00 AC: 0 AN: 24024

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.9
DANN	Benign	0.85
PhyloP100		-0.72
PromoterAI		-0.0053	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs886058665; hg19: chr3-49059329;