7-3301829-C-G

Variant names:

• chr7-3301829-C-G
• rs542888434
• NM_152744.4:c.243C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_152744.4(SDK1):​c.243C>G​(p.Arg81Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,115,002 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (7 hom.)
• Consequence: SDK1 NM_152744.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.238
• Publications: 0 publications found

Genes affected

SDK1 (HGNC:19307): (sidekick cell adhesion molecule 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. The protein contains six immunoglobulin-like domains and thirteen fibronectin type III domains. Fibronectin type III domains are present in both extracellular and intracellular proteins and tandem repeats are known to contain binding sites for DNA, heparin and the cell surface. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

SDK1-AS1 (HGNC:40883): (SDK1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 7-3301829-C-G is Benign according to our data. Variant chr7-3301829-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2657245.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.238 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152744.4. 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
	SDK1	NM_152744.4	MANE Select	c.243C>G	p.Arg81Arg	synonymous	Exon 1 of 45	NP_689957.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDK1	ENST00000404826.7	TSL:1 MANE Select	c.243C>G	p.Arg81Arg	synonymous	Exon 1 of 45	ENSP00000385899.2	Q7Z5N4-1
	SDK1	ENST00000389531.7	TSL:5	c.243C>G	p.Arg81Arg	synonymous	Exon 1 of 44	ENSP00000374182.3	F8W6X9
	SDK1-AS1	ENST00000437354.2	TSL:3	n.224+400G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 311 AN: 148810 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000706

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.00120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000752

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.00146

GnomAD2 exomes AF: 0.00 AC: 0 AN: 44 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00356 AC: 3441 AN: 966098 Hom.: 7 Cov.: 32 AF XY: 0.00366 AC XY: 1663 AN XY: 454290

African (AFR) AF: 0.000262 AC: 5 AN: 19104

American (AMR) AF: 0.00171 AC: 8 AN: 4686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9548

East Asian (EAS) AF: 0.00 AC: 0 AN: 15962

South Asian (SAS) AF: 0.000972 AC: 18 AN: 18518

European-Finnish (FIN) AF: 0.000859 AC: 11 AN: 12804

Middle Eastern (MID) AF: 0.000864 AC: 2 AN: 2316

European-Non Finnish (NFE) AF: 0.00386 AC: 3274 AN: 847566

Other (OTH) AF: 0.00346 AC: 123 AN: 35594

GnomAD4 genome AF: 0.00209 AC: 311 AN: 148904 Hom.: 0 Cov.: 31 AF XY: 0.00173 AC XY: 126 AN XY: 72636

African (AFR) AF: 0.000704 AC: 29 AN: 41164

American (AMR) AF: 0.00120 AC: 18 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5058

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4804

European-Finnish (FIN) AF: 0.000752 AC: 7 AN: 9310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00368 AC: 246 AN: 66878

Other (OTH) AF: 0.00145 AC: 3 AN: 2072

Alfa AF: 0.000637 Hom.: 0

Bravo AF: 0.00178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.63
PhyloP100		-0.24
PromoterAI		0.0030	Neutral
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

Other links and lift over

dbSNP: rs542888434; hg19: chr7-3341461;