chr7-97117880-T-A

Variant names:

• chr7-97117880-T-A
• NM_020186.3:c.157T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_020186.3(SDHAF3):​c.157T>A​(p.Phe53Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,794 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SDHAF3 NM_020186.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.69

Genes affected

SDHAF3 (HGNC:21752): (succinate dehydrogenase complex assembly factor 3) Predicted to be involved in mitochondrial respiratory chain complex II assembly; regulation of gluconeogenesis; and succinate metabolic process. Predicted to be located in mitochondrial matrix. Predicted to be active in mitochondrial intermembrane space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDHAF3	NM_020186.3	c.157T>A	p.Phe53Ile	missense_variant	Exon 1 of 2	ENST00000432641.3	NP_064571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDHAF3	ENST00000432641.3	c.157T>A	p.Phe53Ile	missense_variant	Exon 1 of 2	1	NM_020186.3	ENSP00000414066.2
SDHAF3	ENST00000360382.4	c.157T>A	p.Phe53Ile	missense_variant	Exon 1 of 3	2		ENSP00000353548.4
SDHAF3	ENST00000489852.1	n.180T>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727180

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.070	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.11	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.81
MutPred		0.93		Loss of disorder (P = 0.2038);Loss of disorder (P = 0.2038);
MVP		0.37
MPC		0.53
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.61

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: chr7-96747192;