NM_006819.3:c.672+662T>G

Variant names:

• chr11-64196475-T-G
• rs11607165
• NM_006819.3:c.672+662T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006819.3(STIP1):​c.672+662T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 151,182 control chromosomes in the GnomAD database, including 2,245 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2245 hom., cov: 30)
• Consequence: STIP1 NM_006819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIP1	NM_006819.3	MANE Select	c.672+662T>G		intron	N/A	NP_006810.1
	STIP1	NM_001282652.2		c.813+662T>G		intron	N/A	NP_001269581.1
	STIP1	NM_001282653.2		c.600+662T>G		intron	N/A	NP_001269582.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIP1	ENST00000305218.9	TSL:1 MANE Select	c.672+662T>G		intron	N/A	ENSP00000305958.5
	STIP1	ENST00000358794.9	TSL:1	c.813+662T>G		intron	N/A	ENSP00000351646.5
	STIP1	ENST00000538945.5	TSL:2	c.600+662T>G		intron	N/A	ENSP00000445957.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24552 AN: 151072 Hom.: 2240 Cov.: 30

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.163 AC: 24571 AN: 151182 Hom.: 2245 Cov.: 30 AF XY: 0.164 AC XY: 12120 AN XY: 73784

African (AFR) AF: 0.105 AC: 4317 AN: 41192

American (AMR) AF: 0.277 AC: 4185 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3464

East Asian (EAS) AF: 0.182 AC: 928 AN: 5096

South Asian (SAS) AF: 0.0891 AC: 427 AN: 4792

European-Finnish (FIN) AF: 0.169 AC: 1751 AN: 10334

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11760 AN: 67910

Other (OTH) AF: 0.200 AC: 421 AN: 2106

Alfa AF: 0.170 Hom.: 6773

Bravo AF: 0.171

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.76
DANN	Benign	0.52
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs11607165; hg19: chr11-63963947;