rs1060505002

Variant names:

• chr5-218400-C-A
• rs1060505002
• NM_004168.4:c.45C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-218400-C-A
• chr5-218400-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004168.4(SDHA):​c.45C>A​(p.Arg15Arg) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R15R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SDHA NM_004168.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0430
• Publications: 0 publications found

Genes affected

SDHA (HGNC:10680): (succinate dehydrogenase complex flavoprotein subunit A) This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A pseudogene has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

ENSG00000286001 (HGNC:):

CCDC127 (HGNC:30520): (coiled-coil domain containing 127) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 5-218400-C-A is Benign according to our data. Variant chr5-218400-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3223746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.043 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004168.4. 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
	SDHA	NM_004168.4	MANE Select	c.45C>A	p.Arg15Arg	synonymous	Exon 1 of 15	NP_004159.2
	SDHA	NM_001294332.2		c.45C>A	p.Arg15Arg	synonymous	Exon 1 of 14	NP_001281261.1
	SDHA	NM_001330758.2		c.45C>A	p.Arg15Arg	synonymous	Exon 1 of 13	NP_001317687.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDHA	ENST00000264932.11	TSL:1 MANE Select	c.45C>A	p.Arg15Arg	synonymous	Exon 1 of 15	ENSP00000264932.6
	ENSG00000286001	ENST00000651543.1		n.45C>A		non_coding_transcript_exon	Exon 1 of 24	ENSP00000499215.1
	SDHA	ENST00000874235.1		c.45C>A	p.Arg15Arg	synonymous	Exon 1 of 16	ENSP00000544294.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1294572 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 638952

African (AFR) AF: 0.00 AC: 0 AN: 26496

American (AMR) AF: 0.00 AC: 0 AN: 22982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19812

East Asian (EAS) AF: 0.00 AC: 0 AN: 30772

South Asian (SAS) AF: 0.00 AC: 0 AN: 63400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3636

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1041480

Other (OTH) AF: 0.00 AC: 0 AN: 53010

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.7
DANN	Benign	0.64
PhyloP100		-0.043
PromoterAI		0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs1060505002; hg19: chr5-218515;