1-243330605-A-T

Variant names:

• chr1-243330605-A-T
• rs2275155
• NM_006642.5:c.1134A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006642.5(SDCCAG8):​c.1134A>T​(p.Glu378Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,592 control chromosomes in the GnomAD database, including 75,398 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5461 hom., cov: 32)
  • Exomes 𝑓: 0.30 (69937 hom.)
• Consequence: SDCCAG8 NM_006642.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.125
• Publications: 39 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00143978).
• BP6: Variant 1-243330605-A-T is Benign according to our data. Variant chr1-243330605-A-T is described in ClinVar as Benign. ClinVar VariationId is 260006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

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.1134A>T	p.Glu378Asp	missense	Exon 10 of 18	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.1230A>T	p.Glu410Asp	missense	Exon 11 of 19	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.840A>T	p.Glu280Asp	missense	Exon 10 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.1134A>T	p.Glu378Asp	missense	Exon 10 of 18	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000435549.1	TSL:1	c.474A>T	p.Glu158Asp	missense	Exon 5 of 11	ENSP00000410200.1	A0A0C4DG71
	SDCCAG8	ENST00000884080.1		c.1230A>T	p.Glu410Asp	missense	Exon 11 of 19	ENSP00000554139.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39858 AN: 151898 Hom.: 5463 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.265

GnomAD2 exomes AF: 0.294 AC: 73899 AN: 251280 AF XY: 0.308

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.192

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.304 AC: 444396 AN: 1461576 Hom.: 69937 Cov.: 35 AF XY: 0.311 AC XY: 225884 AN XY: 727104

African (AFR) AF: 0.193 AC: 6447 AN: 33476

American (AMR) AF: 0.199 AC: 8891 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 9218 AN: 26126

East Asian (EAS) AF: 0.188 AC: 7450 AN: 39692

South Asian (SAS) AF: 0.454 AC: 39180 AN: 86254

European-Finnish (FIN) AF: 0.286 AC: 15278 AN: 53416

Middle Eastern (MID) AF: 0.380 AC: 2192 AN: 5768

European-Non Finnish (NFE) AF: 0.304 AC: 337621 AN: 1111740

Other (OTH) AF: 0.300 AC: 18119 AN: 60380

GnomAD4 genome AF: 0.262 AC: 39851 AN: 152016 Hom.: 5461 Cov.: 32 AF XY: 0.264 AC XY: 19650 AN XY: 74292

African (AFR) AF: 0.194 AC: 8035 AN: 41452

American (AMR) AF: 0.214 AC: 3275 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1215 AN: 3472

East Asian (EAS) AF: 0.186 AC: 962 AN: 5172

South Asian (SAS) AF: 0.455 AC: 2187 AN: 4810

European-Finnish (FIN) AF: 0.276 AC: 2911 AN: 10546

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20330 AN: 67970

Other (OTH) AF: 0.264 AC: 556 AN: 2108

Alfa AF: 0.268 Hom.: 1789

Bravo AF: 0.252

TwinsUK AF: 0.307 AC: 1138

ALSPAC AF: 0.304 AC: 1172

ESP6500AA AF: 0.191 AC: 843

ESP6500EA AF: 0.308 AC: 2645

ExAC AF: 0.297 AC: 36107

Asia WGS AF: 0.322 AC: 1121 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	3	Senior-Loken syndrome 7 (3)
-	-	2	Bardet-Biedl syndrome 16 (2)
-	-	2	not provided (2)
-	-	1	Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.13
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.16
Sift	Benign	0.14	T
Sift4G	Benign	0.089	T
Polyphen		0.12	B
Vest4		0.17
MutPred		0.023		Gain of MoRF binding (P = 0.0851)
MPC		0.052
ClinPred		0.016	T
GERP RS		0.25
Varity_R		0.13
gMVP		0.16
Mutation Taster		=89/11	polymorphism (auto)

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: rs2275155; hg19: chr1-243493907; COSMIC: COSV59405589;