rs771462907

Variant names:

• chr19-35995319-C-A
• NM_001042631.3:c.45C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35995319-C-A
• chr19-35995319-C-G
• chr19-35995319-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001042631.3(SDHAF1):​c.45C>A​(p.Tyr15*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,395,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y15Y) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SDHAF1 NM_001042631.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82

Genes affected

SDHAF1 (HGNC:33867): (succinate dehydrogenase complex assembly factor 1) The succinate dehydrogenase (SDH) complex (or complex II) of the mitochondrial respiratory chain is composed of 4 individual subunits. The protein encoded by this gene resides in the mitochondria, and is essential for SDH assembly, but does not physically associate with the complex in vivo. Mutations in this gene are associated with SDH-defective infantile leukoencephalopathy (mitochondrial complex II deficiency).[provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHAF1	NM_001042631.3	c.45C>A	p.Tyr15*	stop_gained	Exon 1 of 1	ENST00000378887.4	NP_001036096.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHAF1	ENST00000378887.4	c.45C>A	p.Tyr15*	stop_gained	Exon 1 of 1	6	NM_001042631.3	ENSP00000368165.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1395748 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690022

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.62
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	0.75
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
Vest4		0.29
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36486221;