chr11-64194312-A-G

Variant names:

• chr11-64194312-A-G
• rs143704701
• NM_006819.3:c.343A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006819.3(STIP1):​c.343A>G​(p.Met115Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: STIP1 NM_006819.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.34
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06536588).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006819.3. 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
	STIP1	NM_006819.3	MANE Select	c.343A>G	p.Met115Val	missense	Exon 3 of 14	NP_006810.1	P31948-1
	STIP1	NM_001282652.2		c.484A>G	p.Met162Val	missense	Exon 3 of 14	NP_001269581.1	P31948-2
	STIP1	NM_001282653.2		c.271A>G	p.Met91Val	missense	Exon 3 of 14	NP_001269582.1	P31948-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIP1	ENST00000305218.9	TSL:1 MANE Select	c.343A>G	p.Met115Val	missense	Exon 3 of 14	ENSP00000305958.5	P31948-1
	STIP1	ENST00000358794.9	TSL:1	c.484A>G	p.Met162Val	missense	Exon 3 of 14	ENSP00000351646.5	P31948-2
	STIP1	ENST00000543847.1	TSL:1	c.343A>G	p.Met115Val	missense	Exon 3 of 5	ENSP00000442704.1	F5H783

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461682 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111954

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.50
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.0096
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.075	N
PhyloP100		5.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.56	N
REVEL	Benign	0.054
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.15
MVP		0.17
MPC		0.50
ClinPred		0.54	D
GERP RS		5.6
Varity_R		0.28
gMVP		0.40
Mutation Taster		=57/43	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: rs143704701; hg19: chr11-63961784;