11-64193149-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006819.3(STIP1):c.81C>T(p.Tyr27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,614,234 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (8 hom.)
• Consequence: STIP1 NM_006819.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.36

Genes affected

STIP1 (HGNC:11387): (stress induced phosphoprotein 1) STIP1 is an adaptor protein that coordinates the functions of HSP70 (see HSPA1A; MIM 140550) and HSP90 (see HSP90AA1; MIM 140571) in protein folding. It is thought to assist in the transfer of proteins from HSP70 to HSP90 by binding both HSP90 and substrate-bound HSP70. STIP1 also stimulates the ATPase activity of HSP70 and inhibits the ATPase activity of HSP90, suggesting that it regulates both the conformations and ATPase cycles of these chaperones (Song and Masison, 2005 [PubMed 16100115]).[supplied by OMIM, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-64193149-C-T is Benign according to our data. Variant chr11-64193149-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 784215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.36 with no splicing effect.
• BS2: High AC in GnomAd at 365 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIP1	NM_006819.3	c.81C>T	p.Tyr27=	synonymous_variant	2/14	ENST00000305218.9
STIP1	NM_001282652.2	c.222C>T	p.Tyr74=	synonymous_variant	2/14
STIP1	NM_001282653.2	c.81C>T	p.Tyr27=	synonymous_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIP1	ENST00000305218.9	c.81C>T	p.Tyr27=	synonymous_variant	2/14	1	NM_006819.3	P1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 365 AN: 152224 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00369

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00233 AC: 586 AN: 251492 Hom.: 3 AF XY: 0.00236 AC XY: 321 AN XY: 135922

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000694

Gnomad ASJ exome AF: 0.00486

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00235

Gnomad FIN exome AF: 0.00157

Gnomad NFE exome AF: 0.00337

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00327 AC: 4777 AN: 1461892 Hom.: 8 Cov.: 31 AF XY: 0.00324 AC XY: 2353 AN XY: 727248

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.00562

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00259

Gnomad4 FIN exome AF: 0.00174

Gnomad4 NFE exome AF: 0.00368

Gnomad4 OTH exome AF: 0.00278

GnomAD4 genome AF: 0.00240 AC: 365 AN: 152342 Hom.: 1 Cov.: 32 AF XY: 0.00224 AC XY: 167 AN XY: 74500

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00369

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00308 Hom.: 0

Bravo AF: 0.00209

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00213

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 29, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2022	STIP1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	8.5
Dann	Benign	0.22

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: rs151183233; hg19: chr11-63960621; COSMIC: COSV59441053; COSMIC: COSV59441053;