rs886038571

Variant names:

• chr1-243344325-A-G
• rs886038571
• NM_006642.5:c.1467A>G
• SDCCAG8 p.Lys489Lys

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006642.5(SDCCAG8):​c.1467A>G​(p.Lys489Lys) variant causes a synonymous change. 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDCCAG8 NM_006642.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.65
• Publications: 1 publications found

Genes affected

SDCCAG8 (HGNC:10671): (SHH signaling and ciliogenesis regulator SDCCAG8) This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy. [provided by RefSeq, Oct 2010]

SDCCAG8 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 16

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• ciliopathy

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-243344325-A-G is Benign according to our data. Variant chr1-243344325-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 260007.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006642.5. 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
	SDCCAG8	NM_006642.5	MANE Select	c.1467A>G	p.Lys489Lys	synonymous	Exon 12 of 18	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.1563A>G	p.Lys521Lys	synonymous	Exon 13 of 19	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.1173A>G	p.Lys391Lys	synonymous	Exon 12 of 18	NP_001337178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.1467A>G	p.Lys489Lys	synonymous	Exon 12 of 18	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000435549.1	TSL:1	c.807A>G	p.Lys269Lys	synonymous	Exon 7 of 11	ENSP00000410200.1	A0A0C4DG71
	SDCCAG8	ENST00000884080.1		c.1563A>G	p.Lys521Lys	synonymous	Exon 13 of 19	ENSP00000554139.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.8
DANN	Benign	0.85
PhyloP100		4.7
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs886038571;

hg19: chr1-243507627;