12-10631058-G-C

Variant summary

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

The NM_018423.3(STYK1):c.438C>G(p.Leu146=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 1,613,822 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00031 (1 hom.)
• Consequence: STYK1 NM_018423.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29

Genes affected

STYK1 (HGNC:18889): (serine/threonine/tyrosine kinase 1) Receptor protein tyrosine kinases, like STYK1, play important roles in diverse cellular and developmental processes, such as cell proliferation, differentiation, and survival (Liu et al., 2004 [PubMed 15150103]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 12-10631058-G-C is Benign according to our data. Variant chr12-10631058-G-C is described in ClinVar as [Benign]. Clinvar id is 768519.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STYK1	NM_018423.3	c.438C>G	p.Leu146=	synonymous_variant	5/11	ENST00000075503.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STYK1	ENST00000075503.8	c.438C>G	p.Leu146=	synonymous_variant	5/11	1	NM_018423.3	P1

Frequencies

GnomAD3 genomes AF: 0.00259 AC: 394 AN: 152140 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00865

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.000625 AC: 157 AN: 251176 Hom.: 0 AF XY: 0.000479 AC XY: 65 AN XY: 135774

Gnomad AFR exome AF: 0.00738

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000311 AC: 455 AN: 1461564 Hom.: 1 Cov.: 30 AF XY: 0.000281 AC XY: 204 AN XY: 727056

Gnomad4 AFR exome AF: 0.00798

Gnomad4 AMR exome AF: 0.000604

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000881

Gnomad4 OTH exome AF: 0.000944

GnomAD4 genome AF: 0.00259 AC: 395 AN: 152258 Hom.: 3 Cov.: 31 AF XY: 0.00255 AC XY: 190 AN XY: 74456

Gnomad4 AFR AF: 0.00865

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.000759 Hom.: 0

Bravo AF: 0.00273

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	8.8
Dann	Benign	0.75

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: rs143474286; hg19: chr12-10783657; COSMIC: COSV99312055; COSMIC: COSV99312055;