7-3301829-C-G

Position:

• chr7-3301829-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_152744.4(SDK1):​c.243C>G​(p.Arg81=) 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

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

Verdict is Benign. Variant got -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 id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDK1	NM_152744.4	c.243C>G	p.Arg81=	synonymous_variant	1/45	ENST00000404826.7	NP_689957.3
SDK1-AS1	XR_001744897.3	n.49857+400G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDK1	ENST00000404826.7	c.243C>G	p.Arg81=	synonymous_variant	1/45	1	NM_152744.4	ENSP00000385899	P2
SDK1-AS1	ENST00000437354.1	n.224+400G>C		intron_variant, non_coding_transcript_variant		3
SDK1	ENST00000389531.7	c.243C>G	p.Arg81=	synonymous_variant	1/44	5		ENSP00000374182	A2

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

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

Gnomad4 AFR exome AF: 0.000262

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000972

Gnomad4 FIN exome AF: 0.000859

Gnomad4 NFE exome AF: 0.00386

Gnomad4 OTH exome AF: 0.00346

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

Gnomad4 AFR AF: 0.000704

Gnomad4 AMR AF: 0.00120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.000752

Gnomad4 NFE AF: 0.00368

Gnomad4 OTH AF: 0.00145

Alfa AF: 0.000637 Hom.: 0

Bravo AF: 0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SDK1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs542888434; hg19: chr7-3341461;