rs34146273

Variant names:

• chr7-97181085-C-A
• rs34146273
• NM_020186.3:c.248C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-97181085-C-A
• chr7-97181085-C-T

Variant summary

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

The NM_020186.3(SDHAF3):​c.248C>A​(p.Thr83Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: SDHAF3 NM_020186.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• Publications: 0 publications found

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]

LOC124901704 (HGNC:):

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 (MetaRNN=0.039217353).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020186.3. 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
	SDHAF3	NM_020186.3	MANE Select	c.248C>A	p.Thr83Asn	missense	Exon 2 of 2	NP_064571.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHAF3	ENST00000432641.3	TSL:1 MANE Select	c.248C>A	p.Thr83Asn	missense	Exon 2 of 2	ENSP00000414066.2
	SDHAF3	ENST00000479853.1	TSL:2	n.212C>A		non_coding_transcript_exon	Exon 2 of 2
	SDHAF3	ENST00000360382.4	TSL:2	c.*121C>A		3_prime_UTR	Exon 3 of 3	ENSP00000353548.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461728 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111930

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.79
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.31
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.015
Sift	Benign	0.38	T
Sift4G	Benign	0.45	T
Polyphen		0.17	B
Vest4		0.093
MutPred		0.22		Gain of catalytic residue at T83 (P = 0.0488)
MVP		0.030
MPC		0.25
ClinPred		0.31	T
GERP RS		0.68
Varity_R		0.029
gMVP		0.13
Mutation Taster		=96/4	polymorphism

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: rs34146273; hg19: chr7-96810397;