chr11-64195751-C-A

Variant names:

• chr11-64195751-C-A
• NM_006819.3:c.610C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_006819.3(STIP1):​c.610C>A​(p.Pro204Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: STIP1 NM_006819.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21274754).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIP1	NM_006819.3	c.610C>A	p.Pro204Thr	missense_variant	Exon 5 of 14	ENST00000305218.9	NP_006810.1
STIP1	NM_001282652.2	c.751C>A	p.Pro251Thr	missense_variant	Exon 5 of 14		NP_001269581.1
STIP1	NM_001282653.2	c.538C>A	p.Pro180Thr	missense_variant	Exon 5 of 14		NP_001269582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIP1	ENST00000305218.9	c.610C>A	p.Pro204Thr	missense_variant	Exon 5 of 14	1	NM_006819.3	ENSP00000305958.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.082	.;T;.;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D;T;D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.1	.;M;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.42	N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.14	T;T;T;D
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.0030, 0.39	.;B;.;B
Vest4		0.31
MutPred		0.36		.;Gain of phosphorylation at P204 (P = 1e-04);.;Gain of phosphorylation at P204 (P = 1e-04);
MVP		0.61
MPC		0.55
ClinPred		0.44	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63963223;